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1.
J Intern Med ; 2022 Feb 25.
Article in English | MEDLINE | ID: covidwho-1714240

ABSTRACT

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown. METHODS: Plasma was collected during hospital admission and after 3 months from the NOR-Solidarity trial (n = 181) and analyzed for markers of gut barrier dysfunction and inflammation. At the 3-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analyzed by sequencing the 16S rRNA gene. RESULTS: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal 3 months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2 /fiO2 (P/F ratio) <26.6 kPa. LBP levels remained elevated during and after hospitalization and were associated with low-grade inflammation and respiratory dysfunction after 3 months. CONCLUSION: Respiratory dysfunction after COVID-19 is associated with altered gut microbiota and persistently elevated LBP levels. Our results should be regarded as hypothesis generating, pointing to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317663

ABSTRACT

Background: There is a need for validated clinical risk scores to identify patients at risk of severe disease and to guide decision-making during the covid-19 pandemic. The National Early Warning Score 2 (NEWS2) is widely used in emergency medicine, but so far, no studies have evaluated its use in patients with covid-19. We aimed to study the performance of NEWS2 and compare commonly used clinical risk stratification tools at admission to predict risk of severe disease and in-hospital mortality in patients with covid-19. Methods: This was a prospective cohort study in a public non-university general hospital in the Oslo area, Norway, including a cohort of all 66 patients hospitalised with confirmed SARS-CoV-2 infection from the start of the pandemic;13 who died during hospital stay and 53 who were discharged alive. Data were collected consecutively from March 9 th to April 27 th 2020. The main outcome was the ability of the NEWS2 score and other clinical risk scores at emergency department admission to predict severe disease and in-hospital mortality in covid-19 patients. We calculated sensitivity and specificity with 95% confidence intervals (CIs) for NEWS2 scores ≥5 and ≥6, quick Sequential Organ Failure Assessment (qSOFA) score ≥2, ≥2 Systemic Inflammatory Response Syndrome (SIRS) criteria, and CRB-65 score ≥2. Areas under the curve (AUCs) for the clinical risk scores were compared using DeLong’s test. Results: In total, 66 patients (mean age 67.9 years) were included. Of these, 23% developed severe disease. In-hospital mortality was 20%. Tachypnoea, hypoxemia and confusion at admission were more common in patients developing severe disease. A NEWS2 score ≥6 at admission predicted severe disease with 80.0% sensitivity and 84.3% specificity (Area Under the Curve (AUC) 0.822, 95% confidence interval (CI) 0.690-0.953). NEWS2 was superior to qSOFA score ≥2 (AUC 0.624, 95% CI 0.446-0.810, p<0.05) and other clinical risk scores for this purpose. Conclusion: NEWS2 score at hospital admission predicted severe disease and in-hospital mortality, and was superior to other widely used clinical risk scores in patients with covid-19.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317660

ABSTRACT

Most SARS-CoV-2 infected individuals develop symptoms that do not require medical management. We hypothesized that pre-existing cross-reactive T cell responses could protect the majority from severe disease. Here we found that CTL and Th cells specific for seasonal human coronaviruses (HCoV) were significantly expanded in recovered COVID-19 donors and that CTL responses were significantly higher than responses to private SARS-CoV-2 peptides not shared with seasonal HCoV. A third of the SARS-CoV-2 peptide:HLA ligandome was matched by highly similar peptide mimics from seasonal HCoV, constituting a common HCoV peptide pool. CTL immunity was significantly skewed to the common HCoV peptide pool in age groups 20-70y, but not >70y-old donors. Over 40% of recovered donors lacked neutralizing antibodies, highlighting the role of T cell immunity in COVID-19. Results suggest a protective pre-acquired T cell immunity to SARS-CoV-2 and identify epitopes that may help boost vaccine responses and ensure broad protection against this family of viruses.Trial Registration: ClinicalTrials.gov: NCT04320732.Funding: This study was funded by The Health-South East Health Authority (Project 29286), the Research Council of Norway (Project 312693), the Oslo University Hospital, the KG Jebsen Foundation (grant 19), the University of Oslo, The Norwegian Cancer Society.Conflict of Interest: The authors declare that we have no competing interests.

4.
Tidsskr Nor Laegeforen ; 141(2)2022 02 01.
Article in English, Norwegian | MEDLINE | ID: covidwho-1674940

ABSTRACT

BACKGROUND: The objective of this article is to summarise the course of illness and treatment for patients with COVID-19 admitted to Bærum Hospital since the start of the pandemic. MATERIAL AND METHOD: We present data from a prospective observational study with the aim of systematising knowledge about patients admitted because of COVID-19. All patients admitted to Bærum Hospital up to and including 28 June 2021 were included. The results are presented for three waves of admissions: 9 March-23 June 2020, 21 September 2020-28 February 2021 and 1 March-28 June 2021. RESULTS: A total of 300 patients, divided into 77, 101 and 122 in the three waves respectively, were admitted because of COVID-19. The number of hospital deaths during the three waves was 14 (18 %), 11 (11 %) and 5 (4 %) respectively. The average age of the patients was 67.6 years in the first wave and 53.3 years in the third wave. Altogether 204 patients (68 %) received medical oxygen or ventilation support, and 31 of these (10 % of all the patients) received invasive ventilation support. Non-invasive ventilation support was used as the highest level of treatment in 4 (8 %), 9 (13 %) and 17 (20 %) patients with respiratory failure in the three waves respectively. In the second and third wave, 125 out of 152 patients with respiratory failure (82 %) were treated with dexamethasone. INTERPRETATION: Differences in patient characteristics and changes to treatment methods, such as the use of dexamethasone and non-invasive ventilation support, may have contributed to the apparent fall in mortality from the first to the third wave. Conditions that are not registered in the study, such as vaccination status, may also have impacted on mortality.


Subject(s)
COVID-19 , Aged , Hospitalization , Hospitals , Humans , Pandemics , SARS-CoV-2
5.
Thrombosis Update ; : 100096, 2022.
Article in English | ScienceDirect | ID: covidwho-1586296

ABSTRACT

Introduction The incidence of thromboembolism during COVID-19 and the use of thromboprophylaxis vary greatly between studies. Only a few studies have investigated the rate of thromboembolism post-discharge. This study determined the 90-day incidence of venous and arterial thromboembolic complications, risk factors for venous thromboembolic events and characterized the use of thromboprophylaxis during and after hospitalization. Materials and methods We retrospectively reviewed medical records for adult patients hospitalized for >24 hours for COVID-19 before May 15, 2020, in ten Norwegian hospitals. We extracted data on demographics, thromboembolic complications, thromboembolic risk factors, and the use of thromboprophylaxis. Cox proportional hazards regression was used to determine risk factors for VTE. Results 550 patients were included. The 90-day incidence of arterial and venous thromboembolism in hospitalized patients was 6.9% (95% CI: 5.1–9.3) overall and 13.8% in the ICU. Male sex (hazard ratio (HR) 7.44, 95% CI 1.73–32.02, p = 0.007) and previous VTE (HR 6.11, 95% CI: 1.74–21.39, p = 0.005) were associated with risk of VTE in multivariable analysis. Thromboprophylaxis was started in 334 patients (61%) with a median duration of 7 days (25th–75th percentile 3–13);in the VTE population 10/23 (43%) started thromboprophylaxis prior to diagnosis. After discharge 20/223 patients received extended thromboprophylaxis and 2/223 (0.7%, 95% CI: 0.3–1.9) had a thromboembolism. Conclusions The 90-day incidence of thromboembolism in COVID-19 patients was 7%, but <1% after discharge. Risk factors were male sex and previous VTE. Most patients received thromboprophylaxis during hospitalization, but only <10% after discharge.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296053

ABSTRACT

BacgroundSuper-infections in COVID-19 patients with acute respiratory distress syndrome (ARDS) on mechanical ventilation were initially reported to be rare. Little is known of their incidence after dexamethasone was introduced as standard care. We aimed to determine the incidence and characteristics of superinfections in mechanically ventilated COVID-19 patients during the course of the COVID-19 pandemic, and explore the possible impact of the introduction of dexamethasone as standard therapy. MethodsIn this national, multi-center, observational, retrospective study we included patients ≥ 18 years admitted from March 1 st 2020 to January 31 st 2021 with polymerase chain reaction (PCR)-confirmed SARSCoV-2 infection treated with invasive mechanical ventilation. Data was collected from electronic health records. Patient characteristics, clinical findings, microbiology, length of stay and 90-day survival were examined with backwards stepwise multiple regression. Results155 patients (115 men, mean age 62 years, range 26-84 years) were included. 73 patients (47%) had a total of 101 superinfections where pneumonia dominated (70%). Superinfections were more commonly observed in patients receiving dexamethasone (67% vs 30%, p<0.0001), and in patients with pre-existing autoimmune disease (18% vs 5%, p<0.01). Invasive fungal infections were reported exclusively in dexamethasone-treated patients [9/72 (13%) vs 0/83 (0%), p<0.0001]. There was no difference in 90-day survival between patients with and patients without superinfections (64% versus 73%, p=0.238). In multiple regression analysis, superinfection was associated with dexamethasone use [OR 5.35 (2.62–11.35), p<0.001], pre-existing autoimmune disease [OR 4.90 (1.50–19.4), p=0.008] and higher lymphocyte count at the time of admission [OR 2.31 (1.23–4.86), p=0.009]. ConclusionIn critically ill COVID-19 patients receiving invasive ventilation, introduction of dexamethasone as standard of care was strongly and independently associated with superinfections. A focus on this complication is warranted when studying alternative anti-inflammatory therapy.

7.
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
12.
Tidsskr Nor Laegeforen ; 140(11)2020 08 18.
Article in Norwegian | MEDLINE | ID: covidwho-724685

ABSTRACT

BACKGROUND: The course of disease, complications and hospital mortality among patients with COVID-19 admitted to Norwegian hospitals has not been widely described. The purpose of this study was to survey patients with COVID-19 admitted to a local hospital. MATERIAL AND METHOD: The data were retrieved from a prospective observational study of all patients admitted with COVID-19 to Bærum Hospital since the start of the coronavirus outbreak. RESULTS: A total of 73 patients with COVID-19 admitted in the period 9 March 2020-7 May 2020 were included. The mean age was 67.9 years, and 43 patients (59 %) were men. The average number of days hospitalised was 10.1. Altogether 19 patients (26 %) had a very severe course of disease, and 14 (19 %) died during their stay in hospital. The mean age among the patients who died was 79.5 years. A total of 49 patients (67 %) had hypoxaemia and required oxygen therapy for an average of 10.1 days. Of these, 9 patients were given invasive respiratory support for a median 18 days. Symptoms of delirium occurred in 26 patients (36 %) and was the most frequent non-respiratory complication. INTERPRETATION: The majority of the patients hospitalised with COVID-19 needed prolonged oxygen therapy, and there was a high incidence of severe complications.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/mortality , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Aged , Betacoronavirus , COVID-19 , Female , Humans , Male , Norway/epidemiology , Pandemics , Prospective Studies , SARS-CoV-2
13.
Scand J Trauma Resusc Emerg Med ; 28(1): 66, 2020 Jul 13.
Article in English | MEDLINE | ID: covidwho-641101

ABSTRACT

BACKGROUND: There is a need for validated clinical risk scores to identify patients at risk of severe disease and to guide decision-making during the covid-19 pandemic. The National Early Warning Score 2 (NEWS2) is widely used in emergency medicine, but so far, no studies have evaluated its use in patients with covid-19. We aimed to study the performance of NEWS2 and compare commonly used clinical risk stratification tools at admission to predict risk of severe disease and in-hospital mortality in patients with covid-19. METHODS: This was a prospective cohort study in a public non-university general hospital in the Oslo area, Norway, including a cohort of all 66 patients hospitalised with confirmed SARS-CoV-2 infection from the start of the pandemic; 13 who died during hospital stay and 53 who were discharged alive. Data were collected consecutively from March 9th to April 27th 2020. The main outcome was the ability of the NEWS2 score and other clinical risk scores at emergency department admission to predict severe disease and in-hospital mortality in covid-19 patients. We calculated sensitivity and specificity with 95% confidence intervals (CIs) for NEWS2 scores ≥5 and ≥ 6, quick Sequential Organ Failure Assessment (qSOFA) score ≥ 2, ≥2 Systemic Inflammatory Response Syndrome (SIRS) criteria, and CRB-65 score ≥ 2. Areas under the curve (AUCs) for the clinical risk scores were compared using DeLong's test. RESULTS: In total, 66 patients (mean age 67.9 years) were included. Of these, 23% developed severe disease. In-hospital mortality was 20%. Tachypnoea, hypoxemia and confusion at admission were more common in patients developing severe disease. A NEWS2 score ≥ 6 at admission predicted severe disease with 80.0% sensitivity and 84.3% specificity (Area Under the Curve (AUC) 0.822, 95% CI 0.690-0.953). NEWS2 was superior to qSOFA score ≥ 2 (AUC 0.624, 95% CI 0.446-0.810, p < 0.05) and other clinical risk scores for this purpose. CONCLUSION: NEWS2 score at hospital admission predicted severe disease and in-hospital mortality, and was superior to other widely used clinical risk scores in patients with covid-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Early Warning Score , Hospital Mortality , Patient Admission , Pneumonia, Viral/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19 , Cohort Studies , Female , Humans , Male , Middle Aged , Norway/epidemiology , Pandemics , Risk Assessment , SARS-CoV-2 , Sensitivity and Specificity , Severity of Illness Index
14.
Tidsskr Nor Laegeforen ; 140(8)2020 05 26.
Article in English, Norwegian | MEDLINE | ID: covidwho-431229

ABSTRACT

BACKGROUND: Emerging reports indicate a high incidence of venous thromboembolism in patients hospitalised for SARS-CoV-2 pneumonia during the spring 2020 pandemic. The pronounced pulmonary and systemic inflammatory responses observed in these patients may contribute to a transient hypercoagulable state. In this setting, pulmonary embolism may cause further respiratory distress and clinical deterioration. CASE PRESENTATION: We describe the clinical course of three patients admitted with SARS-CoV-2 infection and respiratory distress, where pulmonary embolism was detected during the course of the hospitalisation. Two of the cases occurred despite early institution of standard dosage of low molecular weight heparin thromboprophylaxis, and in one case, pulmonary embolism was diagnosed during the convalescent phase of an otherwise benign COVID-19 disease course. INTERPRETATION: These cases highlight the importance of awareness of the potentially increased incidence of venous thromboembolism in COVID-19 disease. Further research is required to establish appropriate clinical management guidelines for prevention of thromboembolic complications in COVID-19.


Subject(s)
Coronavirus Infections , Pandemics , Pneumonia, Viral , Venous Thromboembolism , Aged , Anticoagulants , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Female , Humans , Male , Pneumonia, Viral/complications , Pulmonary Embolism/complications , SARS-CoV-2 , Venous Thromboembolism/complications
15.
Tidsskr Nor Laegeforen ; 140(7)2020 05 05.
Article in English, Norwegian | MEDLINE | ID: covidwho-216815

ABSTRACT

BACKGROUND: The COVID-19 outbreak is presenting the health system with new challenges, and there is a great need for knowledge about symptoms, clinical findings and course of illness in patients admitted to Norwegian hospitals with COVID-19. MATERIAL AND METHOD: In this observational qualitative study, all patients admitted to a Norwegian local hospital (Bærum Hospital) with proven COVID-19 infection were included consecutively from the start of the outbreak. We present here patient characteristics, symptoms, clinical findings, experience of using clinical scoring systems and course of illness based on data in medical records. RESULTS: In the period 9-31 March 2020, 42 patients, of whom 28 (67 %) were men, were admitted to hospital with COVID-19 infection. The median age was 72.5 years (range 30-95). Fever (79 %), reduced general condition (79 %), dyspnoea (69 %) and cough (67 %) were the most common symptoms. A total of nine patients (21 %) had a critical course of illness with treatment in the Intensive Care Department and/or death during their stay in hospital. Patients with a critical course had a higher average score on National Early Warning Score 2 (NEWS2) on admission (7.6 vs 3.3). Only one of the most severely ill patients scored ≥ 2 on the quick Sepsis-related Organ Failure Assessment (qSOFA) on admission. INTERPRETATION: Most patients admitted to our hospital with COVID-19 had a fever and respiratory tract symptoms. A high percentage of patients had a critical course of illness. A NEWS2 score of ≥ 5 on admission may be a useful aid in identifying patients at risk of a critical course of illness, while CRB-65 and qSOFA score ≥ 2 proved to be of little usefulness for this purpose in our material.


Subject(s)
Coronavirus Infections , Critical Illness , Pandemics , Pneumonia, Viral , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Cough/etiology , Dyspnea/etiology , Emergency Service, Hospital , Fever/etiology , Humans , Male , Middle Aged , Norway/epidemiology , Organ Dysfunction Scores , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Retrospective Studies , SARS-CoV-2
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