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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313539

ABSTRACT

Background: In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. Objectives: Analyze plasma cytokines in COVID-19 patients and investigate their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Method: Hospitalized patients (n=34) with confirmed COVID-19 were recruited into a prospective cohort study. Clinical data and blood samples were collected at inclusion and after 2-5 and 7-10 days. RF was defined as PaO2/FiO2 ratio (P/F) <40kPa. Plasma cytokines were analyzed by a Human Cytokine 27-plex assay. Measurements and Results: COVID-19 patients with RF and/or treated in ICU showed overall increased systemic cytokine levels. Plasma IL-6, IL-8, G-CSF, MCP-1, MIP-1α levels were negatively correlated with P/F, whereas combinations of IL-6, IP-10, IL-1ra and MCP-1 showed the best association with RF in ROC analysis (AUC 0.79-0.80, p<0.05). During hospitalization the decline was most significant for IP-10 (P<0.001). Conclusion: Elevated levels of pro-inflammatory cytokines were present in patients with severe COVID-19. IL-6 and MCP-1 were inversely correlated with P/F with the largest AUC in ROC analyses and should be further explored as biomarkers to identify patients at risk for severe RF and as targets for improved treatment strategies.

2.
Ann Intern Med ; 174(9): 1261-1269, 2021 09.
Article in English | MEDLINE | ID: covidwho-1547664

ABSTRACT

BACKGROUND: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. OBJECTIVE: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. DESIGN: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). SETTING: 23 hospitals in Norway. PATIENTS: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. INTERVENTION: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). MEASUREMENTS: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. RESULTS: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. LIMITATION: The trial had no placebo group. CONCLUSION: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. PRIMARY FUNDING SOURCE: National Clinical Therapy Research in the Specialist Health Services, Norway.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Hydroxychloroquine/therapeutic use , Viral Load/drug effects , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Antibodies, Viral/blood , Biomarkers/blood , COVID-19/complications , COVID-19/mortality , Cause of Death , Female , Hospital Mortality , Humans , Inflammation/virology , Male , Middle Aged , Norway/epidemiology , Oropharynx/virology , Respiratory Insufficiency/virology , SARS-CoV-2/immunology , Severity of Illness Index , Standard of Care , Treatment Outcome
3.
Crit Care Explor ; 3(10): e0542, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1450449

ABSTRACT

To examine whether interleukin-6 in critical coronavirus disease 2019 is higher in arterial than in central venous blood, as a sign of predominantly local pulmonal rather than systemic interleukin-6 production. DESIGN: Prospective cohort pilot study with repeated weekly measurements of interleukin-6 in arterial and central venous blood. Respiratory function, assessed with Pao2/Fio2 ratio, was measured at the time of blood sampling. SETTING: ICU at a university hospital. SUBJECTS: Nine adult patients with critical coronavirus disease 2019, actively treated and receiving mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: No difference between arterial and central venous interleukin-6 was found. There was a significant negative relationship between interleukin-6 concentration and P/F ratio in both arterial (p = 0.04) and central venous (p = 0.03) blood. CONCLUSIONS: The absence of an arteriovenous interleukin-6 difference implies that interleukin-6 in critical coronavirus disease 2019 is mainly produced outside the lungs as part of a systemic inflammatory response syndrome and act as a driver of local inflammation and damage in the lungs.

8.
BMC Med ; 19(1): 23, 2021 01 21.
Article in English | MEDLINE | ID: covidwho-1067228

ABSTRACT

BACKGROUND: The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification. METHODS: Training cohorts comprised 1276 patients admitted to King's College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy's and St Thomas' Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models. RESULTS: A baseline model of 'NEWS2 + age' had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites. CONCLUSIONS: NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.


Subject(s)
COVID-19/diagnosis , Early Warning Score , Aged , COVID-19/epidemiology , COVID-19/virology , Cohort Studies , Electronic Health Records , Female , Humans , Male , Middle Aged , Pandemics , Prognosis , SARS-CoV-2/isolation & purification , State Medicine , United Kingdom/epidemiology
10.
Sci Rep ; 10(1): 21697, 2020 12 10.
Article in English | MEDLINE | ID: covidwho-1059940

ABSTRACT

In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. In this study we analyzed plasma cytokines in COVID-19 patients and investigated their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Hospitalized patients (n = 34) with confirmed COVID-19 were recruited into a prospective cohort study. Clinical data and blood samples were collected at inclusion and after 2-5 and 7-10 days. RF was defined as PaO2/FiO2 ratio (P/F) < 40 kPa. Plasma cytokines were analyzed by a Human Cytokine 27-plex assay. COVID-19 patients with RF and/or treated in ICU showed overall increased systemic cytokine levels. Plasma IL-6, IL-8, G-CSF, MCP-1, MIP-1α levels were negatively correlated with P/F, whereas combinations of IL-6, IP-10, IL-1ra and MCP-1 showed the best association with RF in ROC analysis (AUC 0.79-0.80, p < 0.05). During hospitalization the decline was most significant for IP-10 (p < 0.001). Elevated levels of pro-inflammatory cytokines were present in patients with severe COVID-19. IL-6 and MCP-1 were inversely correlated with P/F with the largest AUC in ROC analyses and should be further explored as biomarkers to identify patients at risk for severe RF and as targets for improved treatment strategies.


Subject(s)
COVID-19/blood , Chemokine CCL2/blood , Interleukin-6/blood , Respiratory Insufficiency/blood , SARS-CoV-2/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/complications , Female , Humans , Male , Middle Aged , Prospective Studies , Respiratory Insufficiency/etiology , Severity of Illness Index
11.
Resusc Plus ; 4: 100042, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-885428

ABSTRACT

BACKGROUND: COVID-19 may lead to severe disease, requiring intensive care treatment and challenging the capacity of health care systems. The aim of this study was to compare the ability of commonly used scoring systems for sepsis and pneumonia to predict severe COVID-19 in the emergency department. METHODS: Prospective, observational, single centre study in a secondary/tertiary care hospital in Oslo, Norway. Patients were assessed upon hospital admission using the following scoring systems; quick Sequential Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome criteria (SIRS), National Early Warning Score 2 (NEWS2), CURB-65 and Pneumonia Severity index (PSI). The ratio of arterial oxygen tension to inspiratory oxygen fraction (P/F-ratio) was also calculated. The area under the receiver operating characteristics curve (AUROC) for each scoring system was calculated, along with sensitivity and specificity for the most commonly used cut-offs. Severe disease was defined as death or treatment in ICU within 14 days. RESULTS: 38 of 175 study participants developed severe disease, 13 (7%) died and 29 (17%) had a stay at an intensive care unit (ICU). NEWS2 displayed an AUROC of 0.80 (95% confidence interval 0.72-0.88), CURB-65 0.75 (0.65-0.84), PSI 0.75 (0.65-0.84), SIRS 0.70 (0.61-0.80) and qSOFA 0.70 (0.61-0.79). NEWS2 was significantly better than SIRS and qSOFA in predicating severe disease, and with a cut-off of5 points, had a sensitivity and specificity of 82% and 60%, respectively. CONCLUSION: NEWS2 predicted severe COVID-19 disease more accurately than SIRS and qSOFA, but not significantly better than CURB65 and PSI. NEWS2 may be a useful screening tool in evaluating COVID-19 patients during hospital admission. TRIAL REGISTRATION: : ClinicalTrials.gov Identifier: NCT04345536. (https://clinicaltrials.gov/ct2/show/NCT04345536).

13.
Tidsskr Nor Laegeforen ; 140(11)2020 08 18.
Article in English, Norwegian | MEDLINE | ID: covidwho-724572

ABSTRACT

BACKGROUND: COVID-19 pneumonia can result in severe hypoxaemic respiratory failure that requires intensive medical care. We wished to describe COVID-19 intensive care patients who were treated with and without invasive ventilatory support. MATERIAL AND METHOD: The material was retrieved from the local quality register and comprises data on patients with COVID-19 admitted to the intensive care department at Oslo University Hospital Ullevål from 5 March-28 May 2020. The patients were categorised in three groups on the basis of the treatment they received for respiratory failure (oxygen alone, supplemental non-invasive ventilation (NIV), and intubation/ventilator) and described using descriptive statistics. RESULTS: Of 165 hospitalised COVID-19 patients, a total of 26 (16 %) were treated in our intensive care department. Four of them had do-not-resuscitate-orders and were excluded. The 22 patients included in this study had an average age of 56 years (range 25 to 78 years); 17 (77 %) were men. Eleven patients received ventilator treatment, seven oxygen by mask, and four supplemental NIV. In the ventilator group, as of 28 May 2020 two had died, and the remainder had been discharged alive from the intensive care department, with one remaining hospitalised on a ward. All patients treated with oxygen and NIV were alive and had been discharged from hospital. INTERPRETATION: For many patients with COVID-19 respiratory failure and need for intensive care, increased oxygen and NIV are sufficient, but the need for intubation must be continuously assessed. More than 90 % of actively treated intensive care patients survived.


Subject(s)
Coronavirus Infections/therapy , Noninvasive Ventilation , Pneumonia, Viral/therapy , Respiration, Artificial , Respiratory Insufficiency/therapy , Adult , Aged , Betacoronavirus , COVID-19 , Critical Care , Female , Humans , Intensive Care Units , Male , Middle Aged , Norway , Oxygen/therapeutic use , Pandemics , Respiratory Insufficiency/virology , SARS-CoV-2
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