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1.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1695738

ABSTRACT

Summary Mild, subacute COVID-19 in young people show inflammatory enhancement, but normal pulmonary function. Inflammatory markers are associated with age and male sex, whereas clinical symptoms are associated with age and female sex, but not with objective disease markers. Background Coronavirus Disease 2019 (COVID-19) is widespread among adolescents and young adults across the globe. The present study aimed to compare inflammatory markers, pulmonary function and clinical symptoms across non-hospitalized, 12 – 25 years old COVID-19 cases and non-COVID-19 controls, and to investigate associations between inflammatory markers, clinical symptoms, pulmonary function and background variables in the COVID-19 group. Methods The present paper presents baseline data from an ongoing longitudinal observational cohort study (Long-Term Effects of COVID-19 in Adolescents, LoTECA, ClinicalTrials ID: NCT04686734). A total of 31 plasma cytokines and complement activation products were assayed by multiplex and ELISA methodologies. Pulmonary function and clinical symptoms were investigated by spirometry and questionnaires, respectively. Results A total of 405 COVID-19 cases and 111 non-COVID-19 controls were included. The COVID-19 group had significantly higher plasma levels of IL-1β, IL-4, IL-7, IL-8, IL-12, TNF, IP-10, eotaxin, GM-CSF, bFGF, complement TCC and C3bc, and significantly lower levels of IL-13 and MIP-1α, as compared to controls. Spirometry did not detect any significant differences across the groups. IL-4, IL-7, TNF and eotaxin were negatively associated with female sex;eotaxin and IL-4 were positively associated with age. Clinical symptoms were positively associated with female sex and age, but not with objective disease markers. Conclusions Among non-hospitalized adolescents and young adults with COVID-19 there was significant alterations of plasma inflammatory markers in the subacute stage of the infection. Still, pulmonary function was normal. Clinical symptoms were independent of inflammatory and pulmonary function markers, but positively associated with age and female sex.

2.
J Am Heart Assoc ; 11(3): e023473, 2022 02.
Article in English | MEDLINE | ID: covidwho-1642968

ABSTRACT

Background The extent of cardiac dysfunction post-COVID-19 varies, and there is a lack of data on arrhythmic burden. Methods and Results This was a combined multicenter prospective cohort study and cross-sectional case-control study. Cardiac function assessed by echocardiography in patients with COVID-19 3 to 4 months after hospital discharge was compared with matched controls. The 24-hour ECGs were recorded in patients with COVID-19. A total of 204 patients with COVID-19 consented to participate (mean age, 58.5 years; 44% women), and 204 controls were included (mean age, 58.4 years; 44% women). Patients with COVID-19 had worse right ventricle free wall longitudinal strain (adjusted estimated mean difference, 1.5 percentage points; 95% CI, -2.6 to -0.5; P=0.005) and lower tricuspid annular plane systolic excursion (-0.10 cm; 95% CI, -0.14 to -0.05; P<0.001) and cardiac index (-0.26 L/min per m2; 95% CI, -0.40 to -0.12; P<0.001), but slightly better left ventricle global strain (-0.8 percentage points; 95% CI, 0.2-1.3; P=0.008) compared with controls. Reduced diastolic function was twice as common compared with controls (60 [30%] versus 29 [15%], respectively; odds ratio, 2.4; P=0.001). Having dyspnea or fatigue were not associated with cardiac function. Right ventricle free wall longitudinal strain was worse after intensive care treatment. Arrhythmias were found in 27% of the patients, mainly premature ventricular contractions and nonsustained ventricular tachycardia (18% and 5%, respectively). Conclusions At 3 months after hospital discharge with COVID-19, right ventricular function was mildly impaired, and diastolic dysfunction was twice as common compared with controls. There was little evidence for an association between cardiac function and intensive care treatment, dyspnea, or fatigue. Ventricular arrhythmias were common, but the clinical importance is unknown. Registration URL: http://clinicaltrials.gov. Unique Identifier: NCT04535154.


Subject(s)
Arrhythmias, Cardiac , COVID-19 , Heart Diseases , Arrhythmias, Cardiac/virology , COVID-19/complications , COVID-19/therapy , Case-Control Studies , Cross-Sectional Studies , Female , Heart Diseases/virology , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Time Factors
3.
Sci Rep ; 11(1): 23205, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1545647

ABSTRACT

The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Hydroxychloroquine/adverse effects , Lung Diseases/pathology , Matrix Metalloproteinase 9/metabolism , SARS-CoV-2/drug effects , Viral Load , Adenosine Monophosphate/adverse effects , Aged , Alanine/adverse effects , Antibody Formation , Antimalarials/adverse effects , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , COVID-19/virology , Female , Hospitalization , Humans , Lung Diseases/chemically induced , Lung Diseases/enzymology , Lung Diseases/virology , Male , Middle Aged , Severity of Illness Index
4.
Am Heart J ; 242: 61-70, 2021 12.
Article in English | MEDLINE | ID: covidwho-1356105

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) may cause myocardial injury and myocarditis, and reports of persistent cardiac pathology after COVID-19 have raised concerns of long-term cardiac consequences. We aimed to assess the presence of abnormal cardiovascular resonance imaging (CMR) findings in patients recovered from moderate-to-severe COVID-19, and its association with markers of disease severity in the acute phase. METHODS: Fifty-eight (49%) survivors from the prospective COVID MECH study, underwent CMR median 175 [IQR 105-217] days after COVID-19 hospitalization. Abnormal CMR was defined as left ventricular ejection fraction (LVEF) <50% or myocardial scar by late gadolinium enhancement. CMR indices were compared to healthy controls (n = 32), and to circulating biomarkers measured during the index hospitalization. RESULTS: Abnormal CMR was present in 12 (21%) patients, of whom 3 were classified with major pathology (scar and LVEF <50% or LVEF <40%). There was no difference in the need of mechanical ventilation, length of hospital stay, and vital signs between patients with vs without abnormal CMR after 6 months. Severe acute respiratory syndrome coronavirus 2 viremia and concentrations of inflammatory biomarkers during the index hospitalization were not associated with persistent CMR pathology. Cardiac troponin T and N-terminal pro-B-type natriuretic peptide concentrations on admission, were higher in patients with CMR pathology, but these associations were not significant after adjusting for demographics and established cardiovascular disease. CONCLUSIONS: CMR pathology 6 months after moderate-to-severe COVID-19 was present in 21% of patients and did not correlate with severity of the disease. Cardiovascular biomarkers during COVID-19 were higher in patients with CMR pathology, but with no significant association after adjusting for confounders. TRIAL REGISTRATION: COVID MECH Study ClinicalTrials.gov Identifier: NCT04314232.


Subject(s)
COVID-19/complications , Cicatrix/diagnostic imaging , Heart Diseases/diagnostic imaging , Magnetic Resonance Imaging, Cine/methods , Ventricular Dysfunction, Left/diagnostic imaging , Adult , Aged , Biomarkers/blood , COVID-19/blood , Cicatrix/etiology , Female , Gadolinium , Heart Diseases/blood , Heart Diseases/etiology , Heart Diseases/physiopathology , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prospective Studies , Severity of Illness Index , Stroke Volume , Survivors , Troponin T/blood , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology
5.
Eur Respir J ; 58(2)2021 08.
Article in English | MEDLINE | ID: covidwho-1295410

ABSTRACT

BACKGROUND: This study aimed to describe cardiopulmonary function during exercise 3 months after hospital discharge for COVID-19 and compare groups according to dyspnoea and intensive care unit (ICU) stay. METHODS: Participants with COVID-19 discharged from five large Norwegian hospitals were consecutively invited to a multicentre, prospective cohort study. In total, 156 participants (mean age 56.2 years, 60 females) were examined with a cardiopulmonary exercise test (CPET) 3 months after discharge and compared with a reference population. Dyspnoea was assessed using the modified Medical Research Council (mMRC) dyspnoea scale. RESULTS: Peak oxygen uptake (V'O2  peak) <80% predicted was observed in 31% (n=49). Ventilatory efficiency was reduced in 15% (n=24), while breathing reserve <15% was observed in 16% (n=25). Oxygen pulse <80% predicted was found in 18% (n=28). Dyspnoea (mMRC ≥1) was reported by 47% (n=59). These participants had similar V'O2  peak (p=0.10) but lower mean±sd V'O2  peak·kg-1 % predicted compared with participants without dyspnoea (mMRC 0) (76±16% versus 89±18%; p=0.009) due to higher body mass index (p=0.03). For ICU- versus non-ICU-treated participants, mean±sd V'O2  peak % predicted was 82±15% and 90±17% (p=0.004), respectively. Ventilation, breathing reserve and ventilatory efficiency were similar between the ICU and non-ICU groups. CONCLUSIONS: One-third of participants experienced V'O2  peak <80% predicted 3 months after hospital discharge for COVID-19. Dyspnoeic participants were characterised by lower exercise capacity due to obesity and lower ventilatory efficiency. Ventilation and ventilatory efficiency were similar between ICU- and non-ICU-treated participants.


Subject(s)
COVID-19 , Exercise Tolerance , Exercise Test , Female , Hospitalization , Humans , Middle Aged , Oxygen Consumption , Prospective Studies , SARS-CoV-2
6.
Eur Respir J ; 57(4)2021 Apr.
Article in English | MEDLINE | ID: covidwho-1277911

ABSTRACT

The long-term pulmonary outcomes of coronavirus disease 2019 (COVID-19) are unknown. We aimed to describe self-reported dyspnoea, quality of life, pulmonary function and chest computed tomography (CT) findings 3 months following hospital admission for COVID-19. We hypothesised outcomes to be inferior for patients admitted to intensive care units (ICUs), compared with non-ICU patients.Discharged COVID-19 patients from six Norwegian hospitals were enrolled consecutively in a prospective cohort study. The current report describes the first 103 participants, including 15 ICU patients. The modified Medical Research Council (mMRC) dyspnoea scale, the EuroQol Group's questionnaire, spirometry, diffusing capacity of the lung for carbon monoxide (D LCO), 6-min walk test, pulse oximetry and low-dose CT scan were performed 3 months after discharge.mMRC score was >0 in 54% and >1 in 19% of the participants. The median (25th-75th percentile) forced vital capacity and forced expiratory volume in 1 s were 94% (76-121%) and 92% (84-106%) of predicted, respectively. D LCO was below the lower limit of normal in 24% of participants. Ground-glass opacities (GGO) with >10% distribution in at least one of four pulmonary zones were present in 25% of participants, while 19% had parenchymal bands on chest CT. ICU survivors had similar dyspnoea scores and pulmonary function as non-ICU patients, but higher prevalence of GGO (adjusted OR 4.2, 95% CI 1.1-15.6) and lower performance in usual activities.3 months after admission for COVID-19, one-fourth of the participants had chest CT opacities and reduced diffusing capacity. Admission to ICU was associated with pathological CT findings. This was not reflected in increased dyspnoea or impaired lung function.


Subject(s)
COVID-19 , Quality of Life , Dyspnea , Hospitals , Humans , Lung/diagnostic imaging , Prospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
7.
Br J Haematol ; 194(3): 542-546, 2021 08.
Article in English | MEDLINE | ID: covidwho-1241000

ABSTRACT

Infection with coronavirus disease-2019 (COVID-19) may predispose for venous thromboembolism (VTE). There is wide variation in reported incidence rates of VTE in COVID-19, ranging from 3% to 85%. Therefore, the true incidence of thrombotic complications in COVID-19 is uncertain. Here we present data on the incidence of VTE in both hospitalised and non-hospitalised patients from two ongoing prospective cohort studies. The incidence of VTE after diagnosis of COVID-19 was 3·9% [95% confidence interval (CI): 2·1-7·2] during hospitalisation, 0·9% (95% CI: 0·2-3·1) in the three months after discharge and 0·2% (95% CI: 0·00-1·25) in non-hospitalised patients, suggesting an incidence rate at the lower end of that in previous reports.


Subject(s)
COVID-19/complications , Venous Thromboembolism/etiology , Adult , Aged , Anticoagulants/therapeutic use , COVID-19/diagnosis , Female , Heparin, Low-Molecular-Weight/therapeutic use , Hospitalization , Humans , Incidence , Male , Middle Aged , Prospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Thrombosis/drug therapy , Thrombosis/etiology , Venous Thromboembolism/drug therapy
8.
Int J Environ Res Public Health ; 18(4)2021 02 19.
Article in English | MEDLINE | ID: covidwho-1090344

ABSTRACT

This study assessed the prevalence and determinants of fatigue in a population-based cohort of non-hospitalized subjects 1.5-6 months after COVID-19. It was a mixed postal/web survey of all non-hospitalized patients ≥18 years with a positive PCR for SARS-CoV-2 until 1 June 2020 in a geographically defined area. In total, 938 subjects received a questionnaire including the Chalder fatigue scale (CFQ-11) and the energy/fatigue scale of the RAND-36 questionnaire. We estimated z scores for comparison with general population norms. Determinants were analyzed using multivariable logistic and linear regression analysis. In total, 458 subjects (49%) responded to the survey at median 117.5 days after COVID-19 onset, and 46% reported fatigue. The mean z scores of the CFQ-11 total was 0.70 (95% CI 0.58 to 0.82), CFQ-11 physical 0.66 (0.55 to 0.78), CFQ-11 mental 0.47 (0.35 to 0.59) and RAND-36 energy/fatigue -0.20 (-0.31 to -0.1); all CFQ-11 scores differed from those of the norm population (p < 0.001). Female sex, single/divorced/widowed, short time since symptom debut, high symptom load, and confusion during acute COVID-19 were associated with higher multivariable odds of fatigue. In conclusion, the burden of post-viral fatigue following COVID-19 was high, and higher than in a general norm population. Symptoms of fatigue were most prevalent among women, those having a high symptom load, or confusion during the acute phase.


Subject(s)
COVID-19/complications , Fatigue/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prevalence , Surveys and Questionnaires , Survivors , Young Adult
9.
Int J Environ Res Public Health ; 18(4)2021 02 20.
Article in English | MEDLINE | ID: covidwho-1090339

ABSTRACT

This population-based study assessed the prevalence and determinants of symptom-defined post-traumatic stress disorder (PTSD) in a cohort of hospitalized and non-hospitalized patients about 1.5-6 months after their COVID-19 onset. The data were acquired from two mixed postal/web surveys in June-September 2020 from patients all aged ≥18 years with a positive polymerase chain reaction for severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) until 1 June 2020, comprising both hospitalized and non-hospitalized subjects. The catchment areas of the two included hospitals covers about 17% of the population of Norway. In total, 211 hospitalized and 938 non-hospitalized subjects received invitation. The prevalence of symptom-defined PTSD was assessed using the PTSD checklist for DSM-5 (PCL-5). Determinants of symptom-defined PTSD and PTSD symptoms were analyzed using multivariable logistic and linear regression analysis. In total, 583 (51%) subjects responded at median 116 (range 41-200) days after COVID-19 onset. The prevalence of symptom-defined PTSD was 9.5% in hospitalized and 7.0% in non-hospitalized subjects (p = 0.80). Female sex, born outside of Norway, and dyspnea during COVID-19 were risk factors for persistent PTSD symptoms. In non-hospitalized subjects, previous depression and COVID-19 symptom load were also associated with persistent PTSD symptoms. In conclusion, COVID-19 symptom load, but not hospitalization, was associated with symptom-defined PTSD and PTSD symptom severity.


Subject(s)
COVID-19/psychology , Stress Disorders, Post-Traumatic , Adult , Aged , Female , Humans , Male , Middle Aged , Norway/epidemiology , Prevalence , Risk Factors , Stress Disorders, Post-Traumatic/epidemiology
11.
Thorax ; 76(4): 405-407, 2021 04.
Article in English | MEDLINE | ID: covidwho-961141

ABSTRACT

This study assessed symptoms and their determinants 1.5-6 months after symptom onset in non-hospitalised subjects with confirmed COVID-19 until 1 June 2020, in a geographically defined area. We invited 938 subjects; 451 (48%) responded. They reported less symptoms after 1.5-6 months than during COVID-19; median (IQR) 0 (0-2) versus 8 (6-11), respectively (p<0.001); 53% of women and 67% of men were symptom free, while 16% reported dyspnoea, 12% loss/disturbance of smell, and 10% loss/disturbance of taste. In multivariable analysis, having persistent symptoms was associated with the number of comorbidities and number of symptoms during the acute COVID-19 phase.


Subject(s)
COVID-19/diagnosis , Dyspnea/diagnosis , Dyspnea/epidemiology , Olfaction Disorders/diagnosis , Outpatients , Pandemics , Smell/physiology , Adult , COVID-19/epidemiology , Comorbidity , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Norway/epidemiology , Olfaction Disorders/epidemiology , Olfaction Disorders/physiopathology , SARS-CoV-2 , Surveys and Questionnaires , Time Factors
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