Persistent somatic symptoms are key to individual illness perception at one year after COVID-19 in a cross-sectional analysis of a prospective cohort study

Objective Subjective illness perception (IP) can differ from physician's clinical assessment results. Herein, we explored patient's IP during coronavirus disease 2019 (COVID-19) recovery. Methods Participants of the prospective observation CovILD study (ClinicalTrials.gov: NCT04416100) with persistent somatic symptoms or cardiopulmonary findings one year after COVID-19 were analyzed (n = 74). Explanatory variables included demographic and comorbidity, COVID-19 course and one-year follow-up data of persistent somatic symptoms, physical performance, lung function testing, chest computed tomography and trans-thoracic echocardiography. Factors affecting IP (Brief Illness Perception Questionnaire) one year after COVID-19 were identified by regularized modeling and unsupervised clustering. Results In modeling, 33% of overall IP variance (R2) was attributed to fatigue intensity, reduced physical performance and persistent somatic symptom count. Overall IP was largely independent of lung and heart findings revealed by imaging and function testing. In clustering, persistent somatic symptom count (Kruskal-Wallis test: η2 = 0.31, p < .001), fatigue (η2 = 0.34, p < .001), diminished physical performance (χ2 test, Cramer V effect size statistic: V = 0.51, p < .001), dyspnea (V = 0.37, p = .006), hair loss (V = 0.57, p < .001) and sleep problems (V = 0.36, p = .008) were strongly associated with the concern, emotional representation, complaints, disease timeline and consequences IP dimensions. Conclusion Persistent somatic symptoms rather than abnormalities in cardiopulmonary testing influence IP one year after COVID-19. Modifying IP represents a promising innovative approach to treatment of post-COVID-19 condition. Besides COVID-19 severity, individual IP should guide rehabilitation and psychological therapy decisions.

Persistent somatic symptoms are key to individual illness perception at one year after COVID-19 in a cross-sectional analysis of a prospective cohort study.

OBJECTIVE: Subjective illness perception (IP) can differ from physician's clinical assessment results. Herein, we explored patient's IP during coronavirus disease 2019 (COVID-19) recovery. METHODS: Participants of the prospective observation CovILD study (ClinicalTrials.gov: NCT04416100) with persistent somatic symptoms or cardiopulmonary findings one year after COVID-19 were analyzed (n = 74). Explanatory variables included demographic and comorbidity, COVID-19 course and one-year follow-up data of persistent somatic symptoms, physical performance, lung function testing, chest computed tomography and trans-thoracic echocardiography. Factors affecting IP (Brief Illness Perception Questionnaire) one year after COVID-19 were identified by regularized modeling and unsupervised clustering. RESULTS: In modeling, 33% of overall IP variance (R2) was attributed to fatigue intensity, reduced physical performance and persistent somatic symptom count. Overall IP was largely independent of lung and heart findings revealed by imaging and function testing. In clustering, persistent somatic symptom count (Kruskal-Wallis test: η2 = 0.31, p < .001), fatigue (η2 = 0.34, p < .001), diminished physical performance (χ2 test, Cramer V effect size statistic: V = 0.51, p < .001), dyspnea (V = 0.37, p = .006), hair loss (V = 0.57, p < .001) and sleep problems (V = 0.36, p = .008) were strongly associated with the concern, emotional representation, complaints, disease timeline and consequences IP dimensions. CONCLUSION: Persistent somatic symptoms rather than abnormalities in cardiopulmonary testing influence IP one year after COVID-19. Modifying IP represents a promising innovative approach to treatment of post-COVID-19 condition. Besides COVID-19 severity, individual IP should guide rehabilitation and psychological therapy decisions.

COVID-19 and its continuing burden after 12†months: a longitudinal observational prospective multicentre trial.

Background: Recovery trajectories from coronavirus disease 2019 (COVID-19) call for longitudinal investigation. We aimed to characterise the kinetics and status of clinical, cardiopulmonary and mental health recovery up to 1 year following COVID-19. Methods: Clinical evaluation, lung function testing (LFT), chest computed tomography (CT) and transthoracic echocardiography were conducted at 2, 3, 6 and 12 months after disease onset. Submaximal exercise capacity, mental health status and quality of life were assessed at 12 months. Recovery kinetics and patterns were investigated by mixed-effect logistic modelling, correlation and clustering analyses. Risk of persistent symptoms and cardiopulmonary abnormalities at the 1-year follow-up were modelled by logistic regression. Findings: Out of 145 CovILD study participants, 108 (74.5%) completed the 1-year follow-up (median age 56.5 years; 59.3% male; 24% intensive care unit patients). Comorbidities were present in 75% (n=81). Key outcome measures plateaued after 180 days. At 12 months, persistent symptoms were found in 65% of participants; 33% suffered from LFT impairment; 51% showed CT abnormalities; and 63% had low-grade diastolic dysfunction. Main risk factors for cardiopulmonary impairment included pro-inflammatory and immunological biomarkers at early visits. In addition, we deciphered three recovery clusters separating almost complete recovery from patients with post-acute inflammatory profile and an enrichment in cardiopulmonary residuals from a female-dominated post-COVID-19 syndrome with reduced mental health status. Conclusion: 1 year after COVID-19, the burden of persistent symptoms, impaired lung function, radiological abnormalities remains high in our study population. Yet, three recovery trajectories are emerging, ranging from almost complete recovery to post-COVID-19 syndrome with impaired mental health.

Comparative features and outcomes of major neurological complications of COVID-19.

BACKGROUND AND PURPOSE: The aim of this study was to assess the neurological complications of SARS-CoV-2 infection and compare phenotypes and outcomes in infected patients with and without selected neurological manifestations. METHODS: The data source was a registry established by the European Academy of Neurology during the first wave of the COVID-19 pandemic. Neurologists collected data on patients with COVID-19 seen as in- and outpatients and in emergency rooms in 23 European and seven non-European countries. Prospective and retrospective data included patient demographics, lifestyle habits, comorbidities, main COVID-19 complications, hospital and intensive care unit admissions, diagnostic tests, and outcome. Acute/subacute selected neurological manifestations in patients with COVID-19 were analysed, comparing individuals with and without each condition for several risk factors. RESULTS: By July 31, 2021, 1523 patients (758 men, 756 women, and nine intersex/unknown, aged 16-101 years) were registered. Neurological manifestations were diagnosed in 1213 infected patients (79.6%). At study entry, 978 patients (64.2%) had one or more chronic general or neurological comorbidities. Predominant acute/subacute neurological manifestations were cognitive dysfunction (N = 449, 29.5%), stroke (N = 392, 25.7%), sleep-wake disturbances (N = 250, 16.4%), dysautonomia (N = 224, 14.7%), peripheral neuropathy (N = 145, 9.5%), movement disorders (N = 142, 9.3%), ataxia (N = 134, 8.8%), and seizures (N = 126, 8.3%). These manifestations tended to differ with regard to age, general and neurological comorbidities, infection severity and non-neurological manifestations, extent of association with other acute/subacute neurological manifestations, and outcome. CONCLUSIONS: Patients with COVID-19 and neurological manifestations present with distinct phenotypes. Differences in age, general and neurological comorbidities, and infection severity characterize the various neurological manifestations of COVID-19.

Cognitive dysfunction 1 year after COVID-19: evidence from eye tracking.

Increasing evidence suggests persistent cognitive dysfunction after COVID-19. In this cross-sectional study, frontal lobe function was assessed 12 months after the acute phase of the disease, using tailored eye tracking assessments. Individuals who recovered from COVID-19 made significantly more errors in all eye tracking tasks compared to age/sex-matched healthy controls. Furthermore, patients who were treated as inpatients performed worse compared to outpatients and controls. Our results show impaired inhibitory cortical control in individuals who recovered from COVID-19. The association between disease severity and its sequelae may contribute to a better understanding of post-COVID-19 cognitive function.

Incidence and prevalence of coma in the UK and the USA.

The epidemiology of coma is unknown because case ascertainment with traditional methods is difficult. Here, we used crowdsourcing methodology to estimate the incidence and prevalence of coma in the UK and the USA. We recruited UK and US laypeople (aged ≥18 years) who were nationally representative (i.e. matched for age, gender and ethnicity according to census data) of the UK and the USA, respectively, utilizing a crowdsourcing platform. We provided a description of coma and asked survey participants if they-'right now' or 'within the last year'-had a family member in coma. These participants (UK n = 994, USA n = 977) provided data on 30 387 family members (UK n = 14 124, USA n = 16 263). We found more coma cases in the USA (n = 47) than in the UK (n = 20; P = 0.009). We identified one coma case in the UK (0.007%, 95% confidence interval 0.00-0.04%) on the day of the survey and 19 new coma cases (0.13%, 95% confidence interval 0.08-0.21%) within the preceding year, resulting in an annual incidence of 135/100 000 (95% confidence interval 81-210) and a point prevalence of 7 cases per 100 000 population (95% confidence interval 0.18-39.44) in the UK. We identified five cases in the USA (0.031%, 95% confidence interval 0.01-0.07%) on the day of the survey and 42 new cases (0.26%, 95% confidence interval 0.19-0.35%) within the preceding year, resulting in an annual incidence of 258/100 000 (95% confidence interval 186-349) and a point prevalence of 31 cases per 100 000 population (95% confidence interval 9.98-71.73) in the USA. The five most common causes were stroke, medically induced coma, COVID-19, traumatic brain injury and cardiac arrest. To summarize, for the first time, we report incidence and prevalence estimates for coma across diagnosis types and settings in the UK and the USA using crowdsourcing methods. Coma may be more prevalent in the USA than in the UK, which requires further investigation. These data are urgently needed to expand the public health perspective on coma and disorders of consciousness.

Phenotyping of Acute and Persistent Coronavirus Disease 2019 Features in the Outpatient Setting: Exploratory Analysis of an International Cross-sectional Online Survey.

BACKGROUND: Long COVID, defined as the presence of coronavirus disease 2019 (COVID-19) symptoms ≥28 days after clinical onset, is an emerging challenge to healthcare systems. The objective of the current study was to explore recovery phenotypes in nonhospitalized individuals with COVID-19. METHODS: A dual cohort, online survey study was conducted between September 2020 and July 2021 in the neighboring European regions Tyrol (TY; Austria, n = 1157) and South Tyrol (STY; Italy, n = 893). Data were collected on demographics, comorbid conditions, COVID-19 symptoms, and recovery in adult outpatients. Phenotypes of acute COVID-19, postacute sequelae, and risk of protracted recovery were explored using semi-supervised clustering and multiparameter least absolute shrinkage and selection operator (LASSO) modeling. RESULTS: Participants in the study cohorts were predominantly working age (median age [interquartile range], 43 [31-53] years] for TY and 45 [35-55] years] for STY) and female (65.1% in TY and 68.3% in STY). Nearly half (47.6% in TY and 49.3% in STY) reported symptom persistence beyond 28 days. Two acute COVID-19 phenotypes were discerned: the nonspecific infection phenotype and the multiorgan phenotype (MOP). Acute MOP symptoms encompassing multiple neurological, cardiopulmonary, gastrointestinal, and dermatological symptoms were linked to elevated risk of protracted recovery. The major subset of individuals with long COVID (49.3% in TY; 55.6% in STY) displayed no persistent hyposmia or hypogeusia but high counts of postacute MOP symptoms and poor self-reported physical recovery. CONCLUSIONS: The results of our 2-cohort analysis delineated phenotypic diversity of acute and postacute COVID-19 manifestations in home-isolated patients, which must be considered in predicting protracted convalescence and allocating medical resources.

Who Is at Risk of Poor Mental Health Following Coronavirus Disease-19 Outpatient Management?

Background: Coronavirus Disease-19 (COVID-19) convalescents are at risk of developing a de novo mental health disorder or worsening of a pre-existing one. COVID-19 outpatients have been less well characterized than their hospitalized counterparts. The objectives of our study were to identify indicators for poor mental health following COVID-19 outpatient management and to identify high-risk individuals. Methods: We conducted a binational online survey study with adult non-hospitalized COVID-19 convalescents (Austria/AT: n = 1,157, Italy/IT: n = 893). Primary endpoints were positive screening for depression and anxiety (Patient Health Questionnaire; PHQ-4) and self-perceived overall mental health (OMH) and quality of life (QoL) rated with 4 point Likert scales. Psychosocial stress was surveyed with a modified PHQ stress module. Associations of the mental health and QoL with socio-demographic, COVID-19 course, and recovery variables were assessed by multi-parameter Random Forest and Poisson modeling. Mental health risk subsets were defined by self-organizing maps (SOMs) and hierarchical clustering algorithms. The survey analyses are publicly available (https://im2-ibk.shinyapps.io/mental_health_dashboard/). Results: Depression and/or anxiety before infection was reported by 4.6% (IT)/6% (AT) of participants. At a median of 79 days (AT)/96 days (IT) post-COVID-19 onset, 12.4% (AT)/19.3% (IT) of subjects were screened positive for anxiety and 17.3% (AT)/23.2% (IT) for depression. Over one-fifth of the respondents rated their OMH (AT: 21.8%, IT: 24.1%) or QoL (AT: 20.3%, IT: 25.9%) as fair or poor. Psychosocial stress, physical performance loss, high numbers of acute and sub-acute COVID-19 complaints, and the presence of acute and sub-acute neurocognitive symptoms (impaired concentration, confusion, and forgetfulness) were the strongest correlates of deteriorating mental health and poor QoL. In clustering analysis, these variables defined subsets with a particularly high propensity of post-COVID-19 mental health impairment and decreased QoL. Pre-existing depression or anxiety (DA) was associated with an increased symptom burden during acute COVID-19 and recovery. Conclusion: Our study revealed a bidirectional relationship between COVID-19 symptoms and mental health. We put forward specific acute symptoms of the disease as "red flags" of mental health deterioration, which should prompt general practitioners to identify non-hospitalized COVID-19 patients who may benefit from early psychological and psychiatric intervention. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04661462].

Neurological outcome and quality of life 3 months after COVID-19: A prospective observational cohort study.

BACKGROUND AND PURPOSE: To assess neurological manifestations and health-related quality of life (QoL) 3 months after COVID-19. METHODS: In this prospective, multicenter, observational cohort study we systematically evaluated neurological signs and diseases by detailed neurological examination and a predefined test battery assessing smelling disorders (16-item Sniffin Sticks test), cognitive deficits (Montreal Cognitive Assessment), QoL (36-item Short Form), and mental health (Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Checklist-5) 3 months after disease onset. RESULTS: Of 135 consecutive COVID-19 patients, 31 (23%) required intensive care unit (ICU) care (severe), 72 (53%) were admitted to the regular ward (moderate), and 32 (24%) underwent outpatient care (mild) during acute disease. At the 3-month follow-up, 20 patients (15%) presented with one or more neurological syndromes that were not evident before COVID-19. These included polyneuro/myopathy (n = 17, 13%) with one patient presenting with Guillain-Barré syndrome, mild encephalopathy (n = 2, 2%), parkinsonism (n = 1, 1%), orthostatic hypotension (n = 1, 1%), and ischemic stroke (n = 1, 1%). Objective testing revealed hyposmia/anosmia in 57/127 (45%) patients at the 3-month follow-up. Self-reported hyposmia/anosmia was lower (17%) at 3 months, however, improved when compared to the acute disease phase (44%; p < 0.001). At follow-up, cognitive deficits were apparent in 23%, and QoL was impaired in 31%. Assessment of mental health revealed symptoms of depression, anxiety, and posttraumatic stress disorders in 11%, 25%, and 11%, respectively. CONCLUSIONS: Despite recovery from the acute infection, neurological symptoms were prevalent at the 3-month follow-up. Above all, smelling disorders were persistent in a large proportion of patients.

Factors associated with impaired quality of life three months after being diagnosed with COVID-19.

PURPOSE: To assess patient characteristics associated with health-related quality of life (HR-QoL) and its mental and physical subcategories 3 months after diagnosis with COVID-19. METHODS: In this prospective multicentre cohort study, HR-QoL was assessed in 90 patients using the SF-36 questionnaire (36-item Short Form Health Survey), which consists of 8 health domains that can be divided into a mental and physical health component. Mental health symptoms including anxiety, depression, and post-traumatic stress disorders were evaluated using the Hospital Anxiety and Depression Scale (HADS) and Post-traumatic Stress Disorder Checklist-5 (PCL-5) 3 months after COVID-19. Using descriptive statistics and multivariable regression analysis, we identified factors associated with impaired HR-QoL 3 months after COVID-19 diagnosis. RESULTS: Patients were 55 years of age (IQR, 49-63; 39% women) and were classified as severe (23%), moderate (57%), or mild (20%) according to acute disease severity. HR-QoL was impaired in 28/90 patients (31%). Younger age [per year, adjOR (95%CI) 0.94 (0.88-1.00), p = 0.049], longer hospitalization [per day, adjOR (95%CI) 1.07 (1.01-1.13), p = 0.015], impaired sleep [adjOR (95%CI) 5.54 (1.2-25.61), p = 0.028], and anxiety [adjOR (95%CI) 15.67 (3.03-80.99), p = 0.001) were independently associated with impaired HR-QoL. Twenty-nine percent (n = 26) scored below the normal range on the mental health component of the SF-36 and independent associations emerged for anxiety, depression, and self-reported numbness. Impairments in the physical health component of the SF-36 were reported by 12 (13%) patients and linked to hypogeusia and fatigue. CONCLUSION: Every third patient reported a reduction in HR-QoL 3 months after COVID-19 diagnosis and impairments were more prominent in mental than physical well-being.