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1.
Shock ; 2021 Jan 13.
Article in English | MEDLINE | ID: covidwho-1029247

ABSTRACT

ABSTRACT: The ongoing coronavirus disease 2019 (COVID-19) pandemic has swept over the world and causes thousands of deaths. Although the clinical features of COVID-19 become much clearer than before, there are still further problems with the pathophysiological process and treatments of severe patients. One primary problem is with the paradoxical immune states in severe patients with COVID-19. Studies indicate that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can attack the immune system, manifested as a state of immunosuppression with a decrease in lymphocytes, whereas a state of hyperinflammation, presenting as elevated cytokine levels, is also detected in COVID-19. Therefore, discussing the specific status of immunity in COVID-19 will contribute to the understanding of its pathophysiology and the search for appropriate treatments. Here, we review all the available literature concerning the different immune states in COVID-19 and the underlying pathophysiological mechanisms. In addition, the association between immune states and the development and severity of disease as well as the impact on the selection of immunotherapy strategies are discussed in our review.

2.
Ann Intensive Care ; 11(1): 5, 2021 Jan 09.
Article in English | MEDLINE | ID: covidwho-1015901

ABSTRACT

BACKGROUND: Few specific medications have been proven effective for the treatment of patients with severe coronavirus disease 2019 (COVID-19). Here, we tested whether high-dose vitamin C infusion was effective for severe COVID-19. METHODS: This randomized, controlled, clinical trial was performed at 3 hospitals in Hubei, China. Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the ICU were randomly assigned in as 1:1 ratio to either the high-dose intravenous vitamin C (HDIVC) or the placebo. HDIVC group received 12 g of vitamin C/50 ml every 12 h for 7 days at a rate of 12 ml/hour, and the placebo group received bacteriostatic water for injection in the same way within 48 h of arrival to ICU. The primary outcome was invasive mechanical ventilation-free days in 28 days (IMVFD28). Secondary outcomes were 28-day mortality, organ failure (Sequential Organ Failure Assessment (SOFA) score), and inflammation progression (interleukin-6). RESULTS: Only 56 critical COVID-19 patients were ultimately recruited due to the early control of the outbreak. There was no difference in IMVFD28 between two groups (26.0 [9.0-28.0] in HDIVC vs 22.0 [8.50-28.0] in control, p = 0.57). HDIVC failed to reduce 28-day mortality (P = 0.27). During the 7-day treatment period, patients in the HDIVC group had a steady rise in the PaO2/FiO2 (day 7: 229 vs. 151 mmHg, 95% CI 33 to 122, P = 0.01), which was not observed in the control group. IL-6 in the HDIVC group was lower than that in the control group (19.42 vs. 158.00; 95% CI -301.72 to -29.79; P = 0.04) on day 7. CONCLUSION: This pilot trial showed that HDIVC failed to improve IMVFD28, but might show a potential signal of benefit in oxygenation for critically ill patients with COVID-19 improving PaO2/FiO2 even though.

3.
Crit Care Med ; 48(12): e1358, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1003821
4.
BMJ Open ; 10(12): e040768, 2020 12 07.
Article in English | MEDLINE | ID: covidwho-962846

ABSTRACT

INTRODUCTION: The COVID-19 epidemic grows and there are clinical trials of antivirals. There is an opportunity to complement these trials with investigation of angiotensin II type 1 receptor blockers (ARBs) because an ARB (losartan) was effective in murine influenza pneumonia. METHODS AND ANALYSIS: Our innovative design includes: ARBs; alignment with the WHO Ordinal Scale (primary endpoint) to align with other COVID-19 trials; joint longitudinal analysis; and predictive biomarkers (angiotensins I, 1-7, II and ACE1 and ACE2). Our hypothesis is: ARBs decrease the need for hospitalisation, severity (need for ventilation, vasopressors, extracorporeal membrane oxygenation or renal replacement therapy) or mortality of hospitalised COVID-19 infected adults. Our two-pronged multicentre pragmatic observational cohort study examines safety and effectiveness of ARBs in (1) hospitalised adult patients with COVID-19 and (2) out-patients already on or not on ARBs. The primary outcome will be evaluated by ordinal logistic regression and main secondary outcomes by both joint longitudinal modelling analyses. We will compare rates of hospitalisation of ARB-exposed versus not ARB-exposed patients. We will also determine whether continuing ARBs or not decreases the primary outcome. Based on published COVID-19 cohorts, assuming 15% of patients are ARB-exposed, a total sample size of 497 patients can detect a proportional OR of 0.5 (alpha=0.05, 80% power) comparing WHO scale of ARB-exposed versus non-ARB-exposed patients. ETHICS AND DISSEMINATION: This study has core institution approval (UBC Providence Healthcare Research Ethics Board) and site institution approvals (Health Research Ethics Board, University of Alberta; Comite d'etique de la recerche, CHU Sainte Justine (for McGill University and University of Sherbrook); Conjoint Health Research Ethics Board, University of Calgary; Queen's University Health Sciences & Affiliated Hospitals Research Ethics Board; Research Ethics Board, Sunnybrook Health Sciences Centre; Veritas Independent Research Board (for Humber River Hospital); Mount Sinai Hospital Research Ethics Board; Unity Health Toronto Research Ethics Board, St. Michael's Hospital). Results will be disseminated by peer-review publication and social media releases. TRIAL REGISTRATION NUMBER: NCT04510623.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , /drug therapy , Angiotensin II Type 1 Receptor Blockers/pharmacokinetics , Humans , Logistic Models , Multicenter Studies as Topic , Pandemics , Pragmatic Clinical Trials as Topic , Prospective Studies , Treatment Outcome
5.
Shock ; 2020 Nov 23.
Article in English | MEDLINE | ID: covidwho-944545

ABSTRACT

PURPOSE: We used lung ultrasonography to identify features of COVID-19 pneumonia and to evaluate the prognostic value. MATERIALS AND METHODS: We performed lung ultrasonography on 48 COVID-19 patients in an ICU (Wuhan, China) using a 12-zone method. The associations between lung ultrasonography score, PaO2/FiO2, APACHE II, SOFA, and PaCO2 with 28-day mortality were analyzed and the receiver operator characteristic curve was plotted. RESULTS: 25.9% areas in all scanning zones presented with B7 lines and 23.5% with B3 lines(B-pattern) on lung ultrasonography; 13% areas with confluent B lines(B-pattern), 24.9% in areas with consolidations, and 9.9% in areas with A lines. Pleural effusion was observed in 2.8% of areas. Lung ultrasonography score was negatively correlated with PaO2/FiO2 (n = 48, r = -0.498, P < 0.05) andpositively correlated with APACHE II (n = 48, r = 0.435, P < 0.05). Lung ultrasonography score was independently associated with 28-day mortality. The areas under ROC curves of lung ultrasonography score was 0.735 (95% CI: 0.586-0.844). The sensitivity, specificity, and cutoff values were 0.833, 0.722, and 22.5, respectively. CONCLUSIONS: Lung ultrasonography could be used to assess the severity of COVID-19 pneumonia, and it could also reveal the pathological signs of the disease. The lung ultrasonography score on ICU admission was independently related to the ICU 28-day mortality.

6.
Cell Prolif ; 53(12): e12947, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-933976

ABSTRACT

OBJECTIVES: We aim to explore the safety and feasibility of umbilical cord mesenchymal stem cells (UC-MSCs) transplantation in patients with severe and critically severe coronavirus disease-2019 (COVID-19). METHODS: We conducted a small sample, single arm, pilot trial. In addition to standard therapy, we performed four rounds of transplantation of UC-MSCs in sixteen patients with severe and critically severe COVID-19. We recorded adverse events from enrolment to Day 28. We evaluated the oxygenation index, inflammatory biomarkers, radiological presentations of the disease and lymphocyte subsets count on the 7th day (D7 ± 1 day), the 14th day (D14 ± 1 day) and the 28th day (D28 ± 3 days). RESULTS: There were no infusion-related or allergic reactions. The oxygenation index was improved after transplantation. The mortality of enrolled patients was 6.25%, whereas the historical mortality rate was 45.4%. The level of cytokines estimated varied in the normal range, the radiological presentations (ground glass opacity) were improved and the lymphocyte count and lymphocyte subsets (CD4+ T cells, CD8+ T cells and NK cells) count showed recovery after transplantation. CONCLUSIONS: Intravenous transplantation of UC-MSCs was safe and feasible for treatment of patients with severe and critically severe COVID-19 pneumonia.


Subject(s)
/drug therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , /pathogenicity , Adult , Feasibility Studies , Female , Humans , Male , Middle Aged , Pilot Projects , Safety , Umbilical Cord/cytology
8.
Nat Rev Nephrol ; 16(12): 747-764, 2020 12.
Article in English | MEDLINE | ID: covidwho-872710

ABSTRACT

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.


Subject(s)
Acute Kidney Injury/therapy , Acute Kidney Injury/virology , /therapy , Renal Replacement Therapy/methods , Acute Kidney Injury/diagnosis , Acute Kidney Injury/pathology , Anticoagulants/therapeutic use , Consensus , Humans , Risk Factors
9.
Shock ; 54(5): 644-651, 2020 11.
Article in English | MEDLINE | ID: covidwho-867936

ABSTRACT

INTRODUCTION: Coronavirus disease-2019 (COVID-19) outbreak has spread around the world. However, the dynamic course of critically ill COVID-19 has not been described thoroughly. PATIENTS AND METHODS: We retrospectively analyzed 195 critically ill COVID-19 patients in Hubei province, China, between January 5, 2020 and April 3, 2020. Epidemiologic data, clinical features, treatments, and outcomes were collected and analyzed. RESULTS: Most critically ill patients were older with higher Acute Physiology and Chronic Health Evaluation II scores. After critical illness onset, a total of 181 (92.8%) patients received ventilation support, of which 84 (43.1%) received noninvasive and 97 (49.7%) received invasive mechanic ventilation (IMV). Among the 97 patients with IMV, 28 (28.9%) received prone ventilation, 57 (58.8%) received neuromuscular blocked therapy, and 22 (11.3%) received tracheostomy due to prolonged ventilator use. Early hypoxemia, subsequent hypercapnia, pulmonary hypertension, and finally pulmonary fibrosis were notable in the clinical course of acute respiratory distress syndrome (ARDS). Eighty-nine (45.6%) patients presented with shock. Acute kidney injury (29.7%) and secondary infection (28.2%) were also notable. The overall mortality of critically ill patients at day 28 was 42.1%. Intensive care unit (ICU) mortality was around 33%, as 16 patients died prior to ICU admission. A low PaO2/FiO2 ratio was an independent risk factor for death. High viral load was observed in most non-survivors. CONCLUSION: ARDS and shock were notable in the critical illness of COVID-19. Ventilation support and hemodynamic support were the cornerstones for critical care. High viral load was associated with death of critically ill COVID-19 patients.


Subject(s)
Cardiovascular Agents/therapeutic use , Coronavirus Infections/therapy , Hemodynamics/drug effects , Pneumonia, Viral/therapy , Respiration, Artificial , Aged , Cardiovascular Agents/adverse effects , China/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Critical Illness , Disease Progression , Female , Hospital Mortality , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Respiration, Artificial/adverse effects , Respiration, Artificial/mortality , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Viral Load
10.
Preprint | SSRN | ID: ppcovidwho-1177

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has been widely spread and caused tens of thousands of deaths, mainly in patients with severe COVID-19 br

11.
Preprint | SSRN | ID: ppcovidwho-777

ABSTRACT

Background: Since the end of 2019, coronavirus disease-2019 (COVID-19) outbreak spreads around the world We aimed to share the details of critically ill patien

13.
Preprint | SSRN | ID: ppcovidwho-672

ABSTRACT

Background: The outbreak of 2019 novel coronavirus (COVID-19) has infected many people all around the world We aimed to report the clinical, radiological, and

15.
BMC Infect Dis ; 20(1): 662, 2020 Sep 09.
Article in English | MEDLINE | ID: covidwho-751233

ABSTRACT

BACKGROUND: The outbreak of the novel coronavirus (COVID-19) that was firstly reported in Wuhan, China, with cases now confirmed in more than 100 countries. However, COVID-19 pneumonia with spontaneous pneumothorax is unknown. CASE PRESENTATION: We reported a case of 66-year-old man infected with COVID-19, presenting with fever, cough and myalgia; The patient received supportive and empirical treatment including antiviral treatment, anti-inflammatory treatment, oxygen supply and inhalation therapy; The symptoms, CT images, laboratory results got improved after the treatments, and a throat swab was negative for COVID-19 PCR test; However, on the hospital day 30, the patient presented with a sudden chest pain and dyspnea. CT showed a 30-40% left-sided pneumothorax. Immediate thoracic closed drainage was performed and his dyspnea was rapidly improved. With five more times negative PCR tests for SARS-CoV-2 virus, the patient was discharged and home quarantine. CONCLUSION: This case highlights the importance for clinicians to pay attention to the appearance of spontaneous pneumothorax, especially patients with severe pulmonary damage for a long course, as well as the need for early image diagnose CT and effective treatment once pneumothorax occurs.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Pneumonia, Viral/complications , Pneumothorax/complications , Aged , Betacoronavirus/pathogenicity , Chest Pain/complications , Coronavirus Infections/therapy , Coronavirus Infections/virology , Cough/complications , Drainage , Dyspnea/complications , Fever/complications , Humans , Male , Pandemics , Patient Discharge , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Pneumothorax/therapy
17.
BMJ Open ; 10(7): e039519, 2020 07 08.
Article in English | MEDLINE | ID: covidwho-639482

ABSTRACT

INTRODUCTION: The rapid worldwide spread of COVID-19 has caused a global health crisis. To date, symptomatic supportive care has been the most common treatment. It has been reported that the mechanism of COVID-19 is related to cytokine storms and subsequent immunogenic damage, especially damage to the endothelium and alveolar membrane. Vitamin C (VC), also known as L-ascorbic acid, has been shown to have antimicrobial and immunomodulatory properties. A high dose of intravenous VC (HIVC) was proven to block several key components of cytokine storms, and HIVC showed safety and varying degrees of efficacy in clinical trials conducted on patients with bacterial-induced sepsis and acute respiratory distress syndrome (ARDS). Therefore, we hypothesise that HIVC could be added to the treatment of ARDS and multiorgan dysfunction related to COVID-19. METHODS AND ANALYSIS: The investigators designed a multicentre prospective randomised placebo-controlled trial that is planned to recruit 308 adults diagnosed with COVID-19 and transferred into the intensive care unit. Participants will randomly receive HIVC diluted in sterile water or placebo for 7 days once enrolled. Patients with a history of VC allergy, end-stage pulmonary disease, advanced malignancy or glucose-6-phosphate dehydrogenase deficiency will be excluded. The primary outcome is ventilation-free days within 28 observational days. This is one of the first clinical trials applying HIVC to treat COVID-19, and it will provide credible efficacy and safety data. We predict that HIVC could suppress cytokine storms caused by COVID-19, help improve pulmonary function and reduce the risk of ARDS of COVID-19. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (identifiers: Clinical Ethical Approval No. 2020001). Findings of the trial will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT04264533.


Subject(s)
Ascorbic Acid/administration & dosage , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/drug therapy , Pneumonia, Viral/drug therapy , Vitamins/administration & dosage , Administration, Intravenous , Betacoronavirus , China , Coronavirus Infections/complications , Coronavirus Infections/immunology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Hospital Mortality , Humans , Intensive Care Units , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Respiration, Artificial , Severity of Illness Index , Treatment Outcome
18.
EClinicalMedicine ; 24: 100426, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-628008

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has been widely spread and caused tens of thousands of deaths, especially in patients with severe COVID-19. This analysis aimed to explore risk factors for mortality of severe COVID-19, and establish a scoring system to predict in-hospital deaths. Methods: Patients with COVID-19 were retrospectively analyzed and clinical characteristics were compared. LASSO regression as well as multivariable analysis were used to screen variables and establish prediction model. Findings: A total of 2529 patients with COVID-19 was retrospectively analyzed, and 452 eligible severe COVID-19 were used for finally analysis. In training cohort, the median age was 66•0 years while it was 73•0 years in non-survivors. Patients aged 60-75 years accounted for the largest proportion of infected populations and mortality toll. Anti-SARS-CoV-2 antibodies were monitored up to 54 days, and IgG levels reached the highest during 20-30 days. No differences were observed of antibody levels between severe and non-severe patients. About 60.2% of severe patients had complications. Among acute myocardial injury (AMI), acute kidney injury (AKI) and acute liver injury (ALI), the heart was the earliest injured organ, whereas the time from AKI to death was the shortest. Age, diabetes, coronary heart disease (CHD), percentage of lymphocytes (LYM%), procalcitonin (PCT), serum urea, C reactive protein and D-dimer (DD), were identified associated with mortality by LASSO binary logistic regression. Then multivariable analysis was performed to conclude that old age, CHD, LYM%, PCT and DD remained independent risk factors for mortality. Based on the above variables, a scoring system of COVID-19 (CSS) was established to divide patients into low-risk and high-risk groups. This model displayed good discrimination (AUC=0·919) and calibration (P=0·264). Complications in low-risk and high-risk groups were significantly different (P<0·05). Use of corticosteroids in low-risk groups increased hospital stays by 4·5 days (P=0·036) and durations of disease by 7·5 days (P=0·012) compared with no corticosteroids. Interpretation: Old age, CHD, LYM%, PCT and DD were independently related to mortality. CSS was useful for predicting in-hospital mortality and complications, and it could help clinicians to identify high-risk patients with poor prognosis. Funding: This work was supported by the Key Project for Anti-2019 novel Coronavirus Pneumonia from the Ministry of Science and Technology, China (grant number 2020YFC0845500).

19.
J Med Virol ; 92(11): 2751-2757, 2020 11.
Article in English | MEDLINE | ID: covidwho-596632

ABSTRACT

The outbreak of SARS-CoV-2 has become a pandemic with significant mortality. Published studies described clinical characteristics of the disease contain small cohorts from individual centers or larger series consisting of mixed series from multiple different hospitals. We report here analyses of mortality and disease severity among 402 patients from a single hospital. The cohort includes 297 patients with confirmed and 105 with clinical diagnosis. The latter group consists of cases with inconclusive nucleic acid test but meeting the criteria for clinical diagnosis. Data are compared between sexes and among different age groups. The overall case fatality is 5.2%. However, age at 70 years or older is associated with a significantly higher mortality (17.8%) and higher rate of severe and critical illness (57.5%). Case fatality is 8% in patients 50 years of age or older, and 1.2% in those younger than 50 years. In addition, case fatality is 7.6% in male patients, as opposed to 2.9% in females, demonstrating a clear sex difference.


Subject(s)
/diagnosis , /mortality , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , China , Female , Humans , Male , Middle Aged , Severity of Illness Index , Sex Factors , Young Adult
20.
Crit Care Med ; 48(9): 1289-1295, 2020 09.
Article in English | MEDLINE | ID: covidwho-317610

ABSTRACT

OBJECTIVES: Severe acute respiratory distress syndrome is complicated with coronavirus disease 2019 and extracorporeal membrane oxygenation support may be necessary in severe cases. This study is to summarize the clinical features, extracorporeal membrane oxygenation characteristics, and outcomes of patients with severe acute respiratory syndrome coronavirus 2 pneumonia received extracorporeal membrane oxygenation. DESIGN: Descriptive study from two hospitals. SETTING: The ICUs from university hospitals. PATIENTS: Patients with severe acute respiratory syndrome coronavirus 2 pneumonia received mechanical ventilation, including those underwent extracorporeal membrane oxygenation from Zhongnan Hospital of Wuhan University and Wuhan Pulmonary Hospital from January 8, 2020, to March 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical records, laboratory results, ventilator parameters, and extracorporeal membrane oxygenation-related data were abstracted from the medical records. One-hundred twenty-nine critically ill patients with severe acute respiratory syndrome coronavirus 2 pneumonia were admitted to ICU of the two referral hospitals. Fifty-nine patients received mechanical ventilation and 21 of them received extracorporeal membrane oxygenation support (fourteen from Zhongnan hospital and seven from Wuhan pulmonary hospital). Compared to mechanical ventilation patients without extracorporeal membrane oxygenation support, there was a tendency of decline in mortality but with no significant difference (no-extracorporeal membrane oxygenation group 24/38 [63.2%] vs extracorporeal membrane oxygenation group 12/21 [57.1%]; p = 0.782). For those patients with extracorporeal membrane oxygenation, 12 patients died and nine survived by April 7, 2020. Among extracorporeal membrane oxygenation patients, the PaCO2 prior to extracorporeal membrane oxygenation was lower (54.40 mm Hg [29.20-57.50 mm Hg] vs 63.20 mm Hg [55.40-72.12 mm Hg]; p = 0.006), and pH prior to extracorporeal membrane oxygenation was higher (7.38 [7.28-7.48] vs 7.23 [7.16-7.33]; p = 0.023) in survivors than nonsurvivors. CONCLUSIONS: Extracorporeal membrane oxygenation might be an effective salvage treatment for patients with severe acute respiratory syndrome coronavirus 2 pneumonia associated with severe acute respiratory distress syndrome. Severe CO2 retention and acidosis prior to extracorporeal membrane oxygenation indicated a poor prognosis.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Extracorporeal Membrane Oxygenation , Pneumonia, Viral/therapy , /therapy , Aged , Clinical Laboratory Techniques , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/mortality , Female , Hospitals, University , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Prognosis , Respiration, Artificial , Respiratory Function Tests
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