Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Does a 2-week positive affect intervention facilitate physiological recovery from psychological stressors in young adults?

Trait positive affect has been associated with a lower risk of cardiovascular disease (Boehm & Kubzansky, 2012). One pathway by which positive affect might influence physical health is by buffering against psychological stress and its physiological concomitants (i.e., increases in heart rate and blood pressure). In fact, trait positive affect associates with more complete blood pressure recovery following a psychological stressor (DuPont et al., 2020). Prior work also suggests that increasing momentary positive affect in close proximity to a stressor accelerates cardiovascular and cortisol recovery following the task (e.g., Kraft & Pressman, 2012; Speer & Delgado, 2017). However, no study to date has investigated whether increasing global positive affect – outside of the context of a stressor – can also alter stress physiology. As such, the current study aimed to test whether increasing global levels of positive affect with a 2-week positive psychological intervention would facilitate cardiovascular recovery from a psychological stressor in young adults. Prior to testing the study hypothesis, two pilot studies were conducted that aimed to validate a two-week positive psychological intervention (Study 1; N = 225) and a remote version of the Trier Social Stress Test (Study 2; N = 79; Kirschbaum, Pirke, & Hellhammer, 1993). Unfortunately, the two-week positive psychological intervention failed to increase positive affect in the intervention condition, precluding a test of the overall study hypothesis. In the second pilot study, the remote Trier Social Stress Test elicited emotional reactivity, but did not induce greater cardiovascular reactivity in the stress condition relative to a non-stressful control condition. As such, the final study (Study 3; N = 99) aimed to improve the remote Trier Social Stress Test. Results from the final study indicate that the remote Trier Social Stress Test successfully induced heart rate and blood pressure reactivity in the stress condition relative to controls. Furthermore, the task demonstrated good test-retest reliability when assessed one week later. Although the original study hypothesis could not be tested, developing, and validating an online stress task that can be administered remotely may allow future stress research to include populations that were previously unreachable

Dual Impedance Cardiography: An Inexpensive and Reliable Method to Assess Arterial Stiffness

We describe a relatively low-cost and reliable methodology based on impedance cardiography to assess arterial pulse wave velocity. Pulse wave velocity is an important index of vascular health that relates to autonomic function and risk for cardiovascular disease. This methodology lends itself to broader use in psychophysiology, behavioral medicine, and allied fields of study

An Online Trier Social Stress Paradigm to Evoke Affective and Cardiovascular Responses

In response to the COVID-19 pandemic, prior studies have modified the Trier Social Stress Test to be conducted remotely. The current report aimed to extend these studies to test whether a remote Trier Social Stress Test (rTSST) can elicit (a) affective, (b) blood pressure, and (c) heart rate responses relative to a control condition and whether these responses were reliable when assessed one week later. Participants (N = 99, 19.7 ± 3.5 years, 55% female) were randomized to a control or stress condition. Controls completed easier versions of the tasks with a single, friendly researcher. Stress participants performed more difficult versions of the task in front of two judges who participants believed were rating their performance. Blood pressure and heart rate were measured every two minutes throughout, while affect was assessed at baseline, after the final task, and following recovery. The rTSST was feasible to administer with minimal technical issues reported. Results suggest that lower positive affect and higher negative affect were reported during the tasks in the stress condition relative to controls. Similarly, stress participants had higher cardiovascular responses during the tasks relative to controls, except that blood pressure was not elevated during mental arithmetic in stress participants relative to controls. Cardiovascular responses demonstrated good test-retest reliability when assessed one week later, especially when computed using area under the curve methods. Overall, a rTSST can be used to elicit affective and cardiovascular reactivity and provides an opportunity to include participants previously unreachable for in-person laboratory procedures

Is stressor-evoked cardiovascular reactivity a pathway linking positive and negative emotionality to carotid intima-media thickness?

Stressor-evoked cardiovascular reactivity, trait positive emotionality, and negative emotionality are all associated with cardiovascular disease. It is unknown, however, whether cardiovascular reactivity may constitute a pathway by which trait positive or negative emotionality relates to disease risk. Accordingly, this study modeled the cross-sectional relationships between trait positive and negative emotionality, stressor-evoked cardiovascular reactivity, and severity of a subclinical vascular marker of cardiovascular risk, carotid artery intima-media thickness (CA-IMT). The sample consisted of healthy, midlife adults free from clinical cardiovascular disease (N = 286; ages 30-54; 50% female). Trait positive and negative emotionality were measured by three questionnaires. Heart rate and blood pressure reactivity were assessed across three stressor tasks. CA-IMT was assessed by ultrasonography. Latent factors of positive and negative emotionality, blood pressure reactivity, heart rate reactivity, and CA-IMT were created using structural equation modeling. Greater negative emotionality was marginally associated with more CA-IMT (β = .21; p = .049), but lower blood pressure reactivity (β = -.19; p = .03). However, heightened blood pressure (β = .21; p = .03), but not heart rate reactivity (β = -.05; p = .75), associated with greater CA-IMT. Positive emotionality was uncorrelated with cardiovascular reactivity (blood pressure: β = -.04; p = .61; heart rate: β = .16; p = .11) and CA-IMT (β = .16; p = .07). Although trait negative emotionality associates with a known marker of cardiovascular disease risk, independent of positive emotionality, it is unlikely via a stressor-evoked cardiovascular reactivity pathway

Does an Online Positive Psychological Intervention Improve Positive Affect in Young Adults During the COVID-19 Pandemic?

Meta-analyses indicate that positive psychological interventions are effective at increasing positive affect, as well as reducing anxiety and depression; however, it is unclear how well these effects generalize during periods of high stress. Therefore, the current study tested whether a 2-week online positive psychological intervention delivered during the COVID-19 pandemic, a naturalistic stressor, (1) increased positive affect; (2) improved psychological well-being, optimism, life satisfaction, perceived social support, and loneliness; (3) and reduced negative affect in college students, a group known to have high pandemic distress. Participants (N = 250; 76.9% female) ages 18-45 were recruited from the University of Pittsburgh undergraduate subject pool between September and November of 2020. Participants were randomized to the online positive psychological intervention or active control condition and stratified by trait positive affect, sex, and year in college. Participants in both conditions completed one writing activity every other day for two consecutive weeks. Control participants documented their activities for that day (e.g., meals, going to gym). Intervention participants chose from six positive psychology activities. All outcome variables were assessed pre- and post-intervention by validated questionnaires. Across both conditions, positive and negative affect decreased from pre- to post-intervention. No other psychological factor differed by condition, time, or their interaction. The current null findings are in line with a more recent meta-analysis indicating that positive psychological interventions may have smaller effects on psychological well-being and depressive symptoms than was reported pre-pandemic. Study findings may suggest reduced efficacy of virtual positive psychological interventions under highly stressful circumstances.Supplementary informationThe online version contains supplementary material available at 10.1007/s42761-022-00148-z

Dual Impedance Cardiography: An Inexpensive and Reliable Method to Assess Arterial Stiffness

Pulse wave velocity (PWV) is a common measure of arterial stiffness. Non-invasive methods to measure PWV are widely used in biomedical studies of aging and cardiovascular disease, but they are rarely used in psychophysiology. Barriers to wider use include the prohibitive costs of specialized equipment and need for trained technicians (e.g., ultrasonographers). Here, we describe an impedance cardiography method to measure PWV. By this method, impedance signals are dually collected from the thorax and calf. Combined with ensemble averaging of vascular signals, this dual impedance cardiography (d-ICG) method allows for the measurement of aortic flow onset and the arrival time of peripheral pulse waveforms to compute PWV. In a community sample of adults (aged 19–78 years), PWV measured with d-ICG exhibited a strong positive correlation with age. Moreover, age-specific mean PWV values were within the normative reference intervals established by large scale studies using other techniques. PWV derived from d-ICG exhibited high test-retest reliability across several days, as well as excellent inter-rater reliability. Lastly, PWV exhibited expected associations with known cardiovascular disease risk factors and indicators of autonomic cardiovascular control. d-ICG is an inexpensive and reliable method to assess arterial stiffness