Minor myocardial scars in association with cardiopulmonary function after COVID-19.

BACKGROUND: Myocardial scars detected by cardiac magnetic resonance imaging (CMR) after COVID-19 have caused concerns regarding potential long-term cardiovascular consequences. Therefore, we wanted to investigate cardiopulmonary functioning in patients with versus without COVID-19-related myocardial scars. METHODS: In this prospective cohort study, CMR was performed approximately 6 months after moderate-to-severe COVID-19. Before (~3 months post-COVID) and after (~12 months post-COVID) the CMR, patients underwent extensive cardiopulmonary testing with cardiopulmonary exercise tests (CPET), 24-hour ECG, echocardiography, and assessment of dyspnea. We excluded participants with overt heart failure. RESULTS: 49 patients with post-COVID CMR had available cardiopulmonary tests at 3 and 12 months after the index hospitalization. Nine (18%) patients had small LGE-detected myocardial scars. Patients with myocardial scars were older (63.2±13.2 vs 56.2±13.2 years) and more frequently men (89% vs 55%) compared to those without scars. Echocardiographic measurements, arrhythmic burden, and CPET results were similar in patients with and without scars, i.e. peak oxygen uptake: 82.1±11.5% vs 76.3±22.5% of predicted (p=0.46). There were no significant associations between myocardial scar and longitudinal changes in cardiopulmonary function from 3 to 12 months. CONCLUSION: Our findings imply that the presence of minor myocardial scars has limited clinical significance with respect to cardiopulmonary function after COVID-19. .

A prospective study of pulmonary outcomes and chest computed tomography in the first year after COVID-19.

COVID-19 primarily affects the respiratory system. We aimed to evaluate how pulmonary outcomes develop after COVID-19 by assessing participants from the first pandemic wave prospectively 3 and 12 months following hospital discharge. Pulmonary outcomes included self-reported dyspnoea assessed with the modified Medical Research Council dyspnoea scale, 6-min walk distance (6MWD), spirometry, diffusing capacity of the lung for carbon monoxide (D LCO), body plethysmography and chest computed tomography (CT). Chest CT was repeated at 12 months in participants with pathological findings at 3 months. The World Health Organization (WHO) ordinal scale for clinical improvement defined disease severity in the acute phase. Of 262 included COVID-19 patients, 245 (94%) and 222 (90%) participants attended the 3- and 12-month follow-up, respectively. Self-reported dyspnoea and 6MWD remained unchanged between the two time points, while D LCO and total lung capacity improved (0.28 mmol·min-1·kPa-1, 95% CI 0.12-0.44, and 0.13 L, 95% CI 0.02-0.24, respectively). The prevalence of fibrotic-like findings on chest CT at 3 and 12 months in those with follow-up chest CT was unaltered. Those with more severe disease had worse dyspnoea, D LCO and total lung capacity values than those with mild disease. There was an overall positive development of pulmonary outcomes from 3 to 12 months after hospital discharge. The discrepancy between the unaltered prevalence of self-reported dyspnoea and the improvement in pulmonary function underscores the complexity of dyspnoea as a prominent factor of long-COVID. The lack of increase in fibrotic-like findings from 3 to 12 months suggests that SARS-CoV-2 does not induce a progressive fibrotic process in the lungs.

Changes in cardiopulmonary exercise capacity and limitations 3 to 12 months after COVID-19.

RATIONALE: To describe cardiopulmonary function during exercise 12 months after hospital discharge for COVID-19, assess the change from 3 to 12 months, and compare the results with matched controls without COVID-19. METHODS: In this prospective, longitudinal, multicentre cohort study, hospitalized COVID-19 patients were examined with a cardiopulmonary exercise test (CPET) 3 and 12 months after discharge. At 3 months 180 performed a successful CPET, and 177 at 12 months (mean age 59.3 years, 85 females). The COVID-19 patients were compared with controls without COVID-19 matched for age, sex, body mass index, and comorbidity. Main outcome was peak oxygen uptake (V'O2peak). RESULTS: Exercise intolerance (V'O2peak <80% predicted) was observed in 23% at 12 months, related to circulatory (28%), ventilatory (17%), and other limitations including deconditioning, and dysfunctional breathing (55%). Estimated mean difference between 3 and 12 months showed significant increases in V'O2peak % predicted (5.0 percent points (pp), 95% CI (3.1 to 6.9), p<0.001), V'O2peak·kg-1% predicted (3.4 pp, (1.6 to 5.1), p<0.001), and oxygen pulse % predicted (4.6 pp, (2.5 to 6.8), p<0.001). V'O2peak was 2440 mL min-1 in COVID-19 patients compared to 2972 mL min-1 in matched controls CONCLUSIONS: One year after hospital discharge for COVID-19, the majority, 77%, had normal exercise capacity. Only every fourth had exercise intolerance and in these circulatory limiting factors were more common than ventilatory. Deconditioning was common. V'O2peak and oxygen pulse improved significantly from 3 months.

A prospective study of pulmonary outcomes and chest CT the first year after COVID-19

COVID-19 primarily affects the respiratory system. We aimed to evaluate how pulmonary outcomes develop after COVID-19 by assessing participants from the first pandemic wave prospectively 3- and 12-months following hospital discharge. Pulmonary outcomes included self-reported dyspnoea assessed with the modified Medical Research Council dyspnoea scale (mMRC), 6-minute walking distance (6MWD), spirometry, diffusion capacity of the lungs for carbon monoxide (DLCO), body plethysmography, and chest computed tomography (CT). Chest CT was repeated at 12 months in participants with pathological findings at 3 months. The WHO ordinal scale for clinical improvement defined disease severity in the acute phase. Of 262 included COVID-19 patients, 245 (94%) and 222 (90%) participants attended the 3- and 12-month follow-up, respectively. Self-reported dyspnoea and 6MWD remained unchanged between the two time points, while DLCO and total lung capacity improved (0.28 mmol min−1 kPa−1, 95% CI (0.12–0.44), and 0.13 L, 95% CI (0.02–0.24), respectively). The prevalence of fibrotic-like findings on chest CT at 3 and 12 months in those with follow-up chest CT was unaltered. Those with more severe disease had worse dyspnoea, DLCO,å and TLC values than those with mild disease. There was an overall positive development of pulmonary outcomes from 3 to 12 months after hospital discharge. The discrepancy between the unaltered prevalence of self-reported dyspnoea and the improvement in pulmonary function underscores the complexity of dyspnoea as a prominent factor of long-COVID. The lack of increase in fibrotic-like findings from 3 to 12 months suggests that SARS-CoV-2 does not induce a progressive fibrotic process in the lungs. Even though an overall positive development of lung function was observed between 3 and 12 months after hospitalisation for COVID-19, the prevalence of dyspnoea and fibrotic CT-findings remained unaltered, independent of disease severity in the acute phase.

Cognitive function in non-hospitalized patients 8-13 months after acute COVID-19 infection: A cohort study in Norway.

Studies have reported reduced cognitive function following COVID-19 illness, mostly from hospital settings with short follow-up times. This study recruited non-hospitalized COVID-19 patients from a general population to study prevalence of late cognitive impairment and associations with initial symptoms. We invited patients with PCR-confirmed COVID-19. A postal questionnaire addressed basic demographics, initial COVID-19 symptoms and co-morbidity about 4 months after diagnosis. About 7 months later, we conducted cognitive tests using the Cambridge Neuropsychological Test Automated Battery, comprising four tests for short-term memory, attention and executive function. We present descriptive statistics using z-scores relative to UK population norms and defined impairment as z-score <-1.5. We used multivariable logistic regression with impairment as outcome. Continuous domain scores were analysed by multiple linear regression. Of the initial 458 participants; 305 were invited, and 234 (77%) completed cognitive testing. At median 11 (range 8-13) months after PCR positivity, cognitive scores for short term memory, visuospatial processing, learning and attention were lower than norms (p≤0.001). In each domain, 4-14% were cognitively impaired; 68/232 (29%) were impaired in ≥ 1 of 4 tests. There was no association between initial symptom severity and impairment. Multivariable linear regression showed association between spatial working memory and initial symptom load (6-9 symptoms vs. 0-5, coef. 4.26, 95% CI: 0.65; 7.86). No other dimension scores were associated with symptom load. At median 11 months after out-of-hospital SARS-Cov-2 infection, minor cognitive impairment was seen with little association between COVID-19 symptom severity and outcome.

The course and determinants of post-traumatic stress over 12 months after hospitalization for COVID-19.

Objective: To assess the trajectory of symptoms and symptom-defined post-traumatic stress disorder (PTSD) from 1.5 to 12 months after hospitalization for COVID-19 and determine risk factors for persistent symptoms and PTSD. Methods: This was a prospective cohort study of consecutive patients discharged after hospitalization for COVID-19 before 1 June 2020 in six hospitals in Southern Norway. Symptom-defined PTSD was assessed by the post-traumatic stress disorder (PTSD) checklist for DSM-5 (PCL-5) at 1.5, 3 and/or 12 months after hospitalization, using DSM-5 criteria. Changes in PCL-5 symptom score and the prevalence of PTSD were analyzed with multivariable mixed models. Results: In total, 388 patients were discharged alive, and 251 (65%) participated. Respondents had a mean (SD) age of 58.4 (14.2) years, and 142 (57%) were males. The prevalence of symptom-defined PTSD was 14, 8, and 9% at 1.5, 3, and 12 months, respectively. WHO disease severity for COVID-19 was not associated with PCL-5 scores. Female sex, lower age and non-Norwegian origin were associated with higher PCL-5 scores. The odds ratio (OR) (95%CI) for PTSD was 0.32 (0.12 to 0.83, p = 0.019) at 3 months and 0.38 (0.15 to 0.95, p = 0.039) at 12 months compared to 1.5 months. There was no association between PTSD and WHO severity rating. Conclusions: The level of PTSD symptoms decreased from 1.5 to 3 months after hospitalization, but did not decrease further to 12 months, and there was no association between PTSD symptoms and COVID-19 disease severity.

Cognitive Impairment 13 Months After Hospitalization for COVID-19.

This study assessed cognitive function 13 months after hospital discharge for coronavirus disease 2019 (COVID-19), using computer-based cognitive tests. Compared to population norms, 14%-25% of patients were impaired in each dimension, and 53% had cognitive impairment in 1 or more of 4 tests. There was some association with acute COVID-19 disease severity.

Changes in cardiac structure and function from 3 to 12 months after hospitalization for COVID-19.

BACKGROUND: Cardiac function may be impaired during and early after hospitalization for COVID-19, but little is known about the progression of cardiac dysfunction and the association with postacute COVID syndrome (PACS). METHODS: In a multicenter prospective cohort study, patients who had been hospitalized with COVID-19 were enrolled and comprehensive echocardiography was performed 3 and 12 months after discharge. Twenty-four-hour electrocardiogram (ECG) was performed at 3 and 12 months in patients with arrhythmias at 3 months. RESULTS: In total, 182 participants attended the 3 and 12 months visits (age 58 ± 14 years, 59% male, body mass index 28.2 ± 4.2 kg/m2 ). Of these, 35 (20%) had severe COVID-19 (treatment in the intensive care unit) and 74 (52%) had self-reported dyspnea at 3 months. From 3 to 12 months there were no significant overall changes in any measures of left or right ventricle (LV; RV) structure and function (p > .05 for all), including RV strain (from 26.2 ± 3.9% to 26.5 ± 3.1%, p = .29) and LV global longitudinal strain (from 19.2 ± 2.3% to 19.3 ± 2.3%, p = .64). Changes in echocardiographic parameters from 3 to 12 months did not differ by COVID-19 severity or by the presence of persistent dyspnea (p > .05 for all). Among patients with arrhythmia at 3 months, there was no significant change in arrhythmia burden to 12 months. CONCLUSION: Following COVID-19, cardiac structure and function remained unchanged from 3 to 12 months after the index hospitalization, irrespective of COVID-19 severity and presence of persistent dyspnea. These results suggest that progression of cardiac dysfunction after COVID-19 is rare and unlikely to play an important role in PACS.

Respiratory symptoms and respiratory deaths: A multi-cohort study with 45 years observation time.

This study determined the association between respiratory symptoms and death from respiratory causes over a period of 45 years. In four cohorts of random samples of Norwegian populations with 103,881 participants, 43,731 persons had died per 31 December 2016. In total, 5,949 (14%) had died from respiratory diseases; 2,442 (41%) from lung cancer, 1,717 (29%) chronic obstructive pulmonary disease (COPD), 1,348 (23%) pneumonia, 119 (2%) asthma, 147 (2%) interstitial lung disease and 176 (3%) other pulmonary diseases. Compared with persons without respiratory symptoms the multivariable adjusted hazard ratio (HR) for lung cancer deaths increased with score of breathlessness on effort and cough and phlegm, being 2.6 (95% CI 2.1-3.2) for breathlessness score 3 and 2.1 (95% CI 1.7-2.5) for cough and phlegm score 5. The HR of COPD death was 6.4 (95% CI 5.4-7.7) for breathlessness score 3 and 3.0 (2.4-3.6) for cough and phlegm score 5. Attacks of breathlessness and wheeze score 2 had a HR of 1.6 (1.4-1.9) for COPD death. The risk of pneumonia deaths increased also with higher breathlessness on effort score, but not with higher cough and phlegm score, except for score 2 with HR 1.5 (1.2-1.8). In this study with >2.4 million person-years at risk, a positive association was observed between scores of respiratory symptoms and deaths due to COPD and lung cancer. Respiratory symptoms are thus important risk factors, which should be followed thoroughly by health care practitioners for the benefit of public health.

Time trade-off with someone to live for: impact of having significant others on time trade-off valuations of hypothetical health states.

BACKGROUND: The TTO task involves giving up life years, i.e. living a shorter life, to avoid an undesirable health state. Despite being a hypothetical task, some respondents take other life factors into account when completing the task. This study explored the effect of having children and/or a partner on TTO valuations of hypothetical EQ-5D-5L health states in a valuation study of the general population. METHODS: The study used TTO data collected in a Norwegian EQ-5D-5L valuation study in 2019-2020, by one-to-one pc-assisted interviews following the EQ-VT protocol. We used regression modelling to determine the effect of significant others (having children or a partner) on disutility per health state from the TTO valuations. RESULTS: 430 respondents were included [mean age 43.8 (SD 15.9) years, 58% female, 48% with children, 68% with a partner, 25% with neither children nor partner]. Having children and/or a partner was associated with lowered willingness to trade life years translating to higher elicited health state utilities (p < 0.01). CONCLUSION: Having significant others, or the lack of having significant others, was associated with respondents' valuation of hypothetical health states using TTO, more so than traditional sampling variables such as age and sex. Inadequate representativeness in terms of having significant others could bias health state preference values in valuation studies.

Cardiac Dysfunction and Arrhythmias 3 Months After Hospitalization for COVID-19.

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.

Thromboembolic complications during and after hospitalization for COVID-19: Incidence, risk factors and thromboprophylaxis

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.

Cardiopulmonary exercise capacity and limitations 3†months after COVID-19 hospitalisation.

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.

Incidence of thrombotic complications in hospitalised and non-hospitalised patients after COVID-19 diagnosis.

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.

Prevalence and Determinants of Fatigue after COVID-19 in Non-Hospitalized Subjects: A Population-Based Study.

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.

Prevalence and Risk Factors for Post-Traumatic Stress in Hospitalized and Non-Hospitalized COVID-19 Patients.

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.

Persistent symptoms 1.5-6 months after COVID-19 in non-hospitalised subjects: a population-based cohort study.

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.